Apparatus And Method For Providing Enhanced Heat Transfer From A Body

ABSTRACT

Methods and apparatuses for temperature modification of a patient, or selected regions thereof, including an induced state of hypothermia. The temperature modification is accomplished using an in-dwelling heat exchange catheter within which a fluid heat exchange medium circulates. A heat exchange cassette is attached to the circulatory conduits of the catheter, the heat exchange cassette being sized to engage a cavity within a control unit. The control unit includes a heater/cooler device for providing heated or cooled fluid to a heat exchanger in thermal communication with the fluid heat exchange medium circulating to the heat exchange catheter, a user input device, and a processor connected to receive input from various sensors around the body and the system. A temperature control scheme for ramping the body temperature up or down without overshoot is provided.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/897,637, filed Oct. 4, 2010, now U.S. Pat. No. 8,808,344, which is acontinuation of U.S. application Ser. No. 11/413,564, filed Apr. 27,2006, now U.S. Pat. No. 7,806,915, issued Oct. 5, 2010, which claimsbenefit to U.S. Provisional Application No. 60/695,800, filed Jun. 29,2005, and U.S. Provisional Application No. 60/594,662, filed Apr. 27,2005, the entireties of which are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates generally to medical devices and methodsand, more particularly, to a programmable, microprocessor basedcontroller and method for controlling the temperature and flow of athermal exchange fluid that is circulated through a heat exchangecatheter inserted into a patient's body for the purpose of cooling orwarming at least a portion of the patient's body.

BACKGROUND OF THE INVENTION

Under ordinary circumstances, the thermoregulatory mechanisms of ahealthy human body serve to maintain the body at a constant temperatureof about 37° C. (98.6° F.), a condition sometimes referred to as“normothermia.” To maintain normothermia, the thermoregulatorymechanisms act so that heat lost from the person's body is replaced bythe same amount of heat generated by metabolic activity within the body.For various reasons such as extreme environmental exposure to a coldenvironment or loss of thermoregulatory ability as a result of diseaseor anesthesia, a person may develop a body temperature that is belownormal, a condition known as “hypothermia.” A person may develop acondition that is above normothermia, a condition known as“hyperthermia”, as a result of extreme exposure to a hot environment, ormalfunctioning thermoregulatory mechanisms, the latter being a conditionsometimes called “malignant hyperthermia.” The body may also establish aset point temperature (that is, the temperature which the body'sthermoregulatory mechanisms function to maintain) that is abovenormothermia, a condition usually referred to as “fever.” The presentinvention addresses these and other situations requiring alteration ofat least a portion of a patient's body temperature.

Accidental hypothermia is generally a dangerous condition that may evenbe life threatening, and requires treatment. If severe, for examplewhere the body temperature drops below 30° C., hypothermia may haveserious consequences such as cardiac arrhythmias, inability of the bloodto clot normally, or interference with normal metabolism. If the periodof hypothermia is extensive, the patient may even experience impairedimmune response and increased incidence of infection.

Simple methods for treating accidental hypothermia have been known sincevery early times. Such methods include wrapping the patient in blankets,administering warm fluids by mouth, and immersing the patient in a warmwater bath. If the hypothermia is not too severe, these methods may beeffective. However, wrapping a patient in a blanket depends on theability of the patient's own body to generate heat to re-warm the body.Administering warm fluids by mouth relies on the patient's ability toswallow, and is limited in the temperature of the liquid consumed andthe amount of fluid that may be administered in a limited period oftime. Immersing a patient in warm water is often impractical,particularly if the patient is simultaneously undergoing surgery or someother medical procedure.

More recently, hypothermia may be treated in a more complex fashion.Heated warming blankets may be applied to a patient or warming lampsthat apply heat to the skin of the patient may be used. Heat applied tothe patient's skin, however, has to transmit through the skin byconduction or radiation which may be slow and inefficient, and the bloodflow to the skin may be shut down by the body's thermoregulatoryresponse, and thus, even if the skin is warmed, such mechanisms may beineffective in providing heat to the core of the patient's body. Whenbreathing gases are administered to a patient, for example a patientunder anesthesia, the breathing gases may be warmed. This provides heatrelatively fast to the patient, but the amount of heat that can beadministered without injuring the patient's lungs is very limited. Analternative method of warming a hypothermic patient involves infusing ahot liquid into the patient via an IV infusion, but this is limited bythe amount of liquid that can be infused and the temperature of theliquid.

In extreme situations, a very invasive method may be employed to controlhypothermia. Shunts may be placed into the patient to direct blood fromthe patient through an external machine such as a cardiopulmonary bypass(CPB) machine which includes a heater. In this way, the blood may beremoved from the patient, heated externally, and pumped back into thepatient. Such extreme measures have obvious advantages as toeffectiveness, but also obvious drawbacks as to invasiveness. Thepumping of blood through an external circuit that treats the blood isgenerally quite damaging to the blood, and the procedure is onlypossible in a hospital setting with highly trained personnel operatingthe equipment.

Accidental hyperthermia may also result from various conditions. Wherethe normal thermoregulatory ability of the body is lost, because ofdisease or anesthesia, run-away hyperthermia, also known as malignanthyperthermia, may result. The body may also set a higher than normal setpoint resulting in fever which is a type of hyperthermia. Likehypothermia, accidental hyperthermia is a serious condition that maysometimes be harmful, even fatal. In particular, hyperthermia has beenfound to be neurodestructive, both in itself or in conjunction withother health problems such as traumatic brain injury or stroke, where abody temperature in excess of normal has been shown to result indramatically worse outcomes, even death.

As with hypothermia, when the condition is not too severe, simplemethods for treating the condition exist, such as cold water baths andcooling blankets, or antipyretic drugs such as aspirin or acetaminophen,and for the more extreme cases, more effective but complex and invasivemeans such as cooled breathing gases, cold infusions, and blood cooledduring CPB also exist. These, however, are subject to the limitationsand complications as described above in connection with hypothermia.

Although both hypothermia and hyperthermia may be harmful and requiretreatment in some case, in other cases hyperthermia, and especiallyhypothermia, may be therapeutic or otherwise advantageous, and thereforemay be intentionally induced. For example, periods of cardiac arrest orcardiac insufficiency in heart surgery result in insufficient blood tothe brain and spinal cord, and thus can produce brain damage or othernerve damage.

Hypothermia is recognized in the medical community as an acceptedneuroprotectant and therefore a patient is often kept in a state ofinduced hypothermia. Hypothermia also has similar advantageousprotective ability for treating or minimizing the adverse effects ofcertain neurological diseases or disorders such as head trauma, spinaltrauma and hemorrhagic or ischemic stroke. Moreover, hypothermia hasbeen found to be protective of the kidneys from damage due to exposureto nephrotoxic contrast media, such as is used during vasculatureimaging methods like coronary angiography.

For the above reasons and others, it is sometimes desirable to inducewhole-body or regional hypothermia for the purpose of facilitating orminimizing adverse effects of certain surgical or interventionalprocedures such as open heart surgery, aneurysm repair surgeries,endovascular aneurysm repair procedures, spinal surgeries, or othersurgeries where blood flow to the brain, spinal cord or vital organs maybe interrupted or compromised. Hypothermia has also been found to beadvantageous to protect cardiac muscle tissue after a myocardial infarct(MI).

Current methods of attempting to induce hypothermia generally involveconstant surface cooling, by cooling blanket or by alcohol or ice waterrubs. However, such cooling methods are extremely cumbersome, andgenerally ineffective to cool the body's core. The body's response toalcohol or ice water applied to the surface is to shut down thecirculation of blood through the capillary beds, and to the surface ofthe body generally, and thus to prevent the cold surface from coolingthe core. If the surface cooling works at all, it does so very slowly.There is also an inability to precisely control the temperature of thepatient by this method. Patient safety issues may arise when, forexample, ice water baths are used in the presence of defibrillators andother common hospital equipment.

If the patient is in a surgical setting, the patient may be anesthetizedand cooled by cardiopulmonary bypass as described above. Generally,however, this is only available in the most extreme situations involvinga full surgical team and full surgical suite, and importantly, is onlyavailable for a short period of time because of the damage to the bloodcaused by pumping the blood through the extracorporeal circuit comprisedof pumps and tubing. Generally surgeons do not wish to pump the bloodfor periods longer than 4 hours, and in the case of stroke or traumaticbrain damage, it may be desirable to induce hypothermia for longer thana full day. Because of the direct control of the temperature of a largeamount of blood, this method allows fairly precise control of thepatient's temperature. However, it is this very external manipulation oflarge amounts of the patient's blood that makes long term use of thisprocedure very undesirable.

Means for effectively adding or removing heat to or from the core of thebody that do not involve pumping the blood with an external, mechanicalpump have been suggested. For example, a method of treating hypothermiaor hyperthermia by means of a heat exchange catheter placed in thebloodstream of a patient was described in U.S. Pat. No. 5,486,208 toGinsburg, the complete disclosure of which is incorporated herein byreference. Means of controlling the temperature of a patient bycontrolling such a system is disclosed in U.S. Pat. No. 5,837,003, alsoto Ginsburg, the complete disclosure of which is incorporated herein byreference. A further system for such controlled intervasculartemperature control is disclosed in U.S. Pat. No. 6,620,188 to Ginsburget al., and U.S. Pat. No. 6,849,083 to Ginsburg, the complete disclosureof which is incorporated herein by reference. Those patents andpublication disclose a method of treating or inducing hypothermia byinserting a heat exchange catheter having a heat exchange area includinga balloon with heat exchange fins into the bloodstream of a patient, andcirculating heat exchange fluid through the balloon while the balloon isin contact with the blood to add or remove heat from the bloodstream.(As used herein, a balloon is a structure that is readily inflated underpressure and collapsed under vacuum.)

A number of catheter systems for cooling tissue adjacent the catheter orregulating the temperature of the catheter using the temperature offluid circulating within the catheter are shown in the published art.Some such catheters rely on a reservoir or similar tank for a supply ofheat exchange fluid. For example, U.S. Pat. No. 3,425,419 to Dato, U.S.Pat. No. 5,423,811 to Imran et al., U.S. Pat. No. 5,733,319 to Neilson,et al., and U.S. Pat. No. 6,019,783 to Phillips, et al., disclosecatheters with circulating heat exchange fluid from a tank or reservoir.For such systems that involve a catheter placed in the bloodstream,however, difficulties arise in sterilizing the fluid source between usesand rapidly changing the temperature of a large volume of fluid having asignificant thermal mass.

It has been recognized that certain situations call for more coolingpower than has been available using present systems. For example, it ispostulated that reducing the time to cool a patient's blood immediatelyafter a stroke or coronary event may improve the chance that the patientwill recover, or at least reduce the amount of damage done due toischemia. One way to reduce the time necessary to cool a patient's corebody temperature to a desired target value is to maximize the coolingpower available to remove heat from the patient's blood. However,presently available systems, such as those described above, are limitedin the cooling power they can provide, or are too invasive as describedin the case of heat exchange with extracorporeal circulation.

For the foregoing reasons, there is a need for a rapid and effectivemeans to add or remove heat from the fluid supply for a catheter used tocontrol the body temperature of a patient in an effective and efficientmanner, while avoiding the inadequacies of the prior art methods. Such asystem would rapidly, efficiently and controllably provide for heatingor cooling the temperature of a patient or target tissue, and regulatesthe temperature of the patient or target tissue based on feedback fromthe temperature of the patient or target tissue. It would beparticularly advantageous to provide a system that would reliably supplyincreased cooling power compared to present systems, provide forenhanced removal of heat from a patient's body, decrease the timenecessary to reduce the patient's body temperature to a desired targettemperature, and that may be deployed in both surgical and general wardsof the hospital by at least one operator. The present invention fulfillsthis and other needs.

SUMMARY OF THE INVENTION

The present invention avoids many of the problems of the prior art byproviding an improved system to control the heating and/or cooling of acatheter within a body. The system generally includes a control unitexterior to body, a number of conduits extending from the control unit,and a heat transfer catheter in communication with the control unit viathe conduits. The control unit modulates the temperature of a heattransfer region on the catheter using an advantageous controlmethodology to avoid over-shooting a target temperature. The catheterand conduits preferably define a fluid circulation path, wherein thecontrol unit modulates the temperature of the heat transfer region byadjusting the temperature of a heat transfer fluid within thecirculation path. Desirably, the control unit defines a cavity and theconduits are connected to a cassette that fits within the cavity, thecassette having heat exchanger element through which the heat exchangefluid flows.

In one aspect of the present invention, a controller for controlling thetemperature and flow of heat exchange fluid within a circuit isprovided. The circuit is of a type that includes a heat exchangecatheter, a heat exchanger, and a pump for flowing heat exchange fluidthrough the circuit. The controller includes a heat and/or coldgenerating element in thermal contact with the heat exchanger containingthe heat exchange fluid. A patient sensor is positioned and configuredto generate a signal representing a biophysical condition of thepatient. The microprocessor in the controller receives the signal fromthe patient sensor and responds by controlling the generating element.The control unit further includes a mechanical drive unit for activatingthe pump contained in the circuit, and a safety sensor for detecting afluid parameter in the circuit to generate a safety signalrepresentative of the presence or absence of the fluid parameter. Thesafety signal is transmitted to the microprocessor that responds bycontrolling the operation of the pump. The sensor may be a bubbledetector, and the fluid parameter is gas entrained in the heat exchangefluid. Alternatively, the circuit further comprises a reservoir, and thesensor is a fluid level detector for detecting a low fluid level in thereservoir.

In a still further aspect of the present invention, a heat transfercatheter flow system comprises a heat transfer medium circulation loopincluding a transfer catheter, a heat exchange element, and conduitscoupled to the heat transfer catheter and heat exchange element thatenable circulation of the heat transfer medium therebetween. The systemfurther includes a pump head in contact with heat transfer medium withinthe circulation loop for circulating the medium through the loop. Acassette including the heat exchange element and the pump head mateswith a controller housing a control circuit and a pump motor so that thepump head engages the pump motor. An electronic feedback loop thatdetects back-torque experienced by the pump motor provides feedback to acontrol circuit that in turn controls the speed of the pump motor.

In another aspect, the present invention provides a controller forcontrolling the temperature and flow of heat exchange fluid within acircuit of the type that has a heat exchange catheter, a heat exchangeelement, and a pump for flowing heat exchange fluid through the circuit.The controller includes a heat and/or cold generating element in thermalcontact with the heat exchange element. A mechanical drive unitactivates the pump contained in the circuit to pump the heat exchangefluid. The controller includes a microprocessor connected to controlboth the generating element and the mechanical drive unit. A safetysystem is provided for detecting problems in the circuit. The safetysystem includes a plurality of sensors that generate signals indicativeof respective parameters of the system and/or patient. The signals aretransmitted to the microprocessor that responds by controlling theoperation of the generating element and the mechanical drive unit. Inone embodiment, the safety system includes a sensor for detecting thefluid level within the circuit. In a further embodiment, the safetysystem includes a sensor for detecting the temperature of a locationwithin the patient, and further may include a redundant sensor fordetecting the temperature of a location within the patient wherein amicroprocessor is responsive to a difference in the two sensed patienttemperatures. Furthermore, the safety system may include sensors fordetecting bubbles within the circuit, detecting the operating status ofthe generating element, or detecting the operating status of themechanical drive unit.

The present invention also provides a method of regulating thetemperature of patient, comprising the steps of: providing a heatexchange catheter system including a heat exchange catheter having afluid path therethrough, a pair of conduits fluidly connected to theheat exchange catheter, and a heat exchanger connected via the conduitsto circulate heat exchange medium through the exchange catheter;providing a first controller adapted to couple to the heat exchanger ofthe heat exchange catheter system, the first controller including a heatand/or cold generating element therein for exchanging heat at a firstrate with the heat exchange medium within the heat exchanger; providinga second controller adapted to couple to the heat exchanger of the heatexchange catheter system, the second controller including a heat and/orcold generating element therein for exchanging heat at a second ratewith the heat exchange medium within the heat exchanger; coupling theheat exchange catheter system with the first controller; inserting theheat exchange catheter into the patient; regulating the temperature ofthe patient by exchanging heat at the first rate between the generatingelement of the first controller and the heat exchanger; de-coupling theheat exchange catheter system from the first controller; coupling theheat exchange catheter system with the second controller; and regulatingthe temperature of the patient by exchanging heat at the second ratebetween the generating element of the second controller and the heatexchanger. The first and second controller may actually be the samephysical device, but the method of coupling, decoupling, andsubsequently recoupling the device may provide benefits, for examplewhen the patient is being transported from one location to another, oris undergoing a therapeutic or diagnostic procedure, as described below.

The method may include performing a therapeutic or diagnostic procedureon the patient between the steps of de-coupling the heat exchangecatheter system from the first controller and the step of coupling theheat exchange catheter system with the second controller. Indeed, thefirst controller and the second controller may be the same physicaldevice.

In a still further method of the present invention, the rate of changeof a patient's body temperature is controlled using a heat transfercatheter and associated controller. The transfer catheter has a heattransfer region thereon, and the controller is placed in communicationwith the catheter via conduits. The controller is adapted to elevate ordepress the temperature of the catheter heat transfer region relative tothe body temperature. The patient's body temperature within a bodycavity or in another location is sensed, while the temperature of theheat transfer region is determined. A target temperature is thenselected. The target temperature may be different than the bodytemperature, or may be the same if maintenance of normal patienttemperature is the goal. A ramp rate equal to the time rate of change oftemperature from the body temperature to the target temperature isselected. The temperature of the transfer region of the catheter basedon the ramp rate is set. The method includes monitoring the temperaturedifferential between the target temperature and the body temperature,and reducing the ramp rate when the temperature differential reducesbelow a predetermined threshold. Desirably, the heat transfer catheterand conduits defined a fluid circulation path therethrough, wherein thestep of setting the temperature of the catheter heat transfer regioncomprises setting the temperature of a circulating fluid within thecirculation path. Preferably, the step of determining the temperature ofthe catheter heat transfer region comprises directly or indirectlysensing the temperature of the circulating fluid. A comparison may bemade between the target temperature and the temperature of thecirculating fluid, which is then used to adjust the temperature of thecirculating fluid.

In a further aspect, the present invention provides a system capable ofreducing the temperature of a patient in a controllable and rapidmatter. The system includes an arrangement of heat exchangers, pumps andcooling media that is capable of removing sufficient heat energy so asto be able to maintain the temperature of a primary coolant loop in therange of 0-5 degrees centigrade, even when heat loads are in the rangeof about 400 to about 550 watts.

In yet another aspect, the present invention includes a system foradjusting the temperature of a patient, comprising: a primary fluidcircuit, the circuit including a primary fluid reservoir, a primaryfluid circuit pump, a heater cooler, primary fluid circuit linesconnecting the primary fluid circuit pump to the primary fluid reservoirto the heater/cooler such that a continuous flow path for circulatingprimary fluid from the reservoir to the heater/cooler and back to theprimary fluid reservoir is formed; access points in the primary fluidcircuit, the access points fluidly connecting the primary fluid circuitto a primary fluid circuit side of a heat exchanger, the heat exchangeralso having a secondary fluid circuit side; a heat exchange catheterinsertable within a patient, the catheter configured to increase,decrease or maintain the temperature of the patient; a secondary fluidcircuit for flowing secondary fluid through the secondary circuit sideof the heat exchanger and the heat exchange catheter, the secondaryfluid circuit including a secondary fluid reservoir, and a secondaryfluid circuit pump for flowing a secondary heat exchange fluid from thesecondary fluid reservoir through secondary fluid circuit to the heatexchange catheter and back through the secondary fluid circuit to thesecondary fluid reservoir; at least one fluid sensor configured toprovide a signal representative of a temperature of the primary orsecondary fluid circuit; a patient sensor configured to provide a signalrepresentative of a temperature of the patient; and a controllerconfigured to receive the signals from the patient sensor and theprimary fluid sensor and being responsive to the signals to control theheater/cooler to adjust the temperature of the fluid flowing within thefluid circuits. In yet another aspect, the volume of the primary fluidpathway or circuit increases when the heat exchanger is connected withthe primary fluid pathway or circuit.

In a further aspect, the present invention includes the case wherein thecontroller includes a microprocessor configured to be responsive tosensors and to provide control signals as needed to control theoperation of the system.

In a still further aspect, the present invention includes a power supplyfor supplying power to the system, including the heater/cooler;controller circuitry for controlling the operation of the system, thecontroller circuitry including means for determining if the power supplyis operative and operating within parameters determined to beappropriate, means for monitoring the operation of the system, means fordetermining an error state of the monitored system, and means foralerting an operator of the presence of an error state.

In yet another aspect, the present invention includes the cases whereinthe controller controls the heater/cooler to drive the temperature ofthe fluid in the primary fluid circuit towards a predeterminedtemperature prior to fluidly connecting the heat exchanger to theprimary fluid circuit and wherein the controller controls theheater/cooler to drive the temperature of the fluid in the primary fluidcircuit towards a predetermined temperature prior to initiation oftreatment of a patient.

In a still further aspect of the present invention, the primary fluidcircuit includes temperature sensors disposed in the primary fluidcircuit, the temperature sensors providing signals representative of thetemperature of the primary fluid passing through the access pointsflowing into and out of the primary fluid circuit side of the heatexchanger. Alternatively, the temperature difference between the fluidflowing into and out of the primary fluid circuit side of the heatexchanger is proportional to the heat exchange being delivered to thesecondary fluid circuit, and is representative of the heat exchangebeing delivered to the patient. In yet another alternative aspect, thecontroller is responsive to the signals provided by the temperaturesensors to determine the difference in the temperature of the primaryfluid flowing into and out of the access points, and to provide an alertif the determined difference is indicative of a problem condition, orthe controller is responsive to the signals provided by the temperaturesensors to provide an alert if the signals are indicative of a problemcondition.

In another aspect of the present invention, the secondary fluidreservoir includes an air trap disposed between an inlet to thereservoir and the secondary fluid circuit pump. In one aspect the airtrap is a semi-permeable member permitting at least a portion of thesecondary fluid to flow through the semi-permeable member and in anotheraspect the air trap is formed from foam.

In yet another aspect of the present invention, the secondary fluidcircuit contains a particulate filter. In one aspect, the particulatefilter is a semi-permeable member permitting at least a portion of thesecondary fluid to flow through the semi-permeable member and in anotheraspect the particulate filter is formed from foam for formed from ascreen.

In a further aspect, the present invention also includes a leveldetector disposed in the secondary fluid circuit to detect a level ofthe fluid within the secondary fluid circuit, the level detectorproviding a signal representative of the level of fluid in the secondaryfluid circuit to the controller. In one aspect, the level detector isdisposed in cooperation with the secondary fluid reservoir to detect alevel of the fluid within the secondary fluid reservoir.

In yet another aspect of the present invention, the level detector maybe a bubble detector or an air in line detector.

In yet another aspect of the present invention, the controller sends astart signal to the secondary fluid pump in response to a signal fromthe level detector representative of a predetermined fluid level.Alternatively, the controller may send a stop signal to the secondaryfluid pump in response to a signal from the level detectorrepresentative of a predetermined low fluid level.

In one aspect of the present invention, the secondary fluid circuit pumpand secondary fluid reservoir and heat exchanger are included in acassette configuration that is provided to the operator in a sterilecondition. In a further aspect, the present invention also includes areusable housing in which are disposed the primary fluid reservoir,primary fluid circuit pump, microprocessor and a secondary fluid circuitpump motor, the housing being configured to removably receive thecassette such that the secondary fluid circuit pump releasably engagesthe secondary fluid circuit pump motor.

In yet another aspect of the present invention, the access pointsinclude releasable couplers for releasably coupling the heat exchangerto the primary fluid circuit. In one aspect, the releasable couplersfluidly seal when not connected to the primary fluid circuit to minimizeprimary fluid loss from the primary fluid circuit side of the heatexchanger and the primary fluid circuit.

In another aspect, the present invention includes a quick connectcoupler configured to allow electrical connection of a sensor line to acontroller at about the same time the releasable couplers of the heatexchanger are engaged. This provides for easier and more rapid setup ofthe heat exchanger, which is advantageous during an emergency situation.This arrangement also prevents errors that may occur if a care-giverneglects to connect the sensor line before start up of the system.

In still another aspect of the present invention, the primary fluidcircuit further comprises a check valve for controlling a fluid pressurewithin the primary fluid circuit such that the fluid pressure does notexceed a predetermined value. In yet another aspect, the cassette andcatheter may be disconnected from the primary fluid circuit andconnected to a different primary circuit without compromising sterilityor fluid isolation of the secondary fluid circuit of the cassette andcatheter.

In another aspect of the present invention, the fan/blower output of theheater/cooler is reduced when the controller determines that a sensedtemperature is within a predetermined range. In another aspect, thefan/blower output of the heater/cooler is reduced when the controllerdetermines that the sensed temperature is within a predetermined rangefor a predetermined amount of time. In still another aspect, an outputof the primary and/or secondary fluid pump is reduced when thecontroller determines that a sensed temperature is within apredetermined range. In a still further aspect, the output of theprimary and/or secondary pump is reduced when the controller determinesthat demand for patient temperature change is reduced.

In yet another aspect of the present invention, the primary fluidcircuit is configured such that the majority of volume of primary fluidcontained with the heat exchanger is recovered to the primary fluidreservoir prior to disconnection of the heat exchanger from the primaryfluid circuit.

In another aspect of the present invention, the heat exchanger isprovided to the operator with the primary fluid side pre-filled withprimary fluid. In still another aspect, the heat exchanger is providedto the operator with the secondary fluid side pre-filled with secondaryfluid.

In one aspect of the present invention the heat exchanger when connectedis maintained in electrical isolation from the heater/cooler andelectrical inputs to components of the primary fluid loop.

In another aspect of the present invention, the primary fluid circuitincludes a means for maintaining the electrical conductivity at a valuebelow a predetermined value. In another aspect of the present invention,the means includes a sensor configured to sense an electricalcharacteristic of the fluid within the fluid circuit.

In still another aspect, the present invention includes a priming fluidcircuit for providing secondary heat exchange fluid to the secondaryfluid circuit. In a further aspect, the priming fluid circuit includes aprime line and a vent line, at least of one of the prime line and ventline having a valve, and at least one sensor for determining when thesecondary circuit is sufficiently filled with fluid. In a furtheraspect, at least one of the valves in the prime line and vent line is aclamp that engages the line to obstruct fluid flow in the line. In yetanother aspect, the at least one of the valves in the prime line andvent line are controlled by the controller to initiate and completefilling the secondary fluid circuit with secondary fluid.

In another aspect of the present invention, the access points areconfigured to receive primary circuit fluid to fill the primary fluidreservoir. Still further, at least one of the fluid lines is engagedwith the at least one of the fluid lines of the cassette when thecassette is removably received by the housing.

In still another aspect of the present invention, the controllercontrols the temperature of the primary fluid circuit at a levelsufficient to prevent freezing of the secondary fluid in the secondaryfluid circuit.

In yet another aspect of the present invention the, heat exchangerincludes a pair of intermediate fluid pathways. The two intermediatepathways, a primary intermediate pathway and a secondary intermediatefluid pathway, are physically separated from each other, but are inthermal communication with each other. This provides for the exchange ofheat energy between the intermediate fluid pathways, while preventingthe possibility of contaminating the secondary heat exchange fluid whichmay flow into a patient with primary circuit fluid, which may or may notbe biocompatible. In a further aspect, the physical separation of theintermediate fluid pathways ensures that the primary fluid circuit willnot be contaminated should the secondary fluid circuit be invaded byblood or other bodily fluids. In still another aspect, the intermediatefluid pathways, when connected to their respective primary or secondaryfluid circuits, increase the volume of these circuits.

Other features and advantages of the invention will become apparent fromthe following detailed description, taken in conjunction with theaccompanying drawings, which illustrate, by way of example, the featuresof the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a patient undergoing treatment using asystem in accordance with the present invention;

FIG. 2 is a schematic illustration of a disposable heat exchangecassette attached to a heat exchange catheter and an external fluidsource, and positioned for insertion into a suitable opening in are-usable control unit of the present invention,

FIGS. 3A-3B together show a flowchart of a control scheme of the heatexchange system of the present invention;

FIG. 4 is a graph of the sensed temperature of a target tissue or bodyfluid over time under the influence of the control scheme of FIGS.3A-3B;

FIG. 5A is a perspective view of an exemplary re-usable control unit ofthe present invention;

FIG. 5B is a perspective view of an upper portion of the control unit ofFIG. 5A;

FIG. 5C is a plan view of an exemplary control panel for the controlunit of FIG. 5A;

FIG. 6 is a schematic view of an embodiment of the system of the presentinvention showing a heat exchanger in fluid communication with apositive pressure side of a primary fluid circuit pump;

FIG. 7 is a schematic view of another embodiment of the system of thepresent invention showing the heat exchanger in fluid communication witha negative pressure side of the primary fluid circuit pump;

FIG. 8 is a schematic diagram of exemplary components of the presentinvention, illustrating communication and feedback interconnectionstherebetween;

FIG. 9 is an exploded view of an embodiment of the heat exchangecassette of the present invention;

FIG. 10 is a perspective view of the embodiment of FIG. 9;

FIG. 10A is an enlarged perspective view of a portion of the embodimentof FIG. 10;

FIG. 11A is an exploded perspective view of a cassette portion of theembodiment of FIG. 9 showing an exterior view of the cassette portion;

FIG. 11B is an exploded perspective view of the cassette portion of theembodiment of FIG. 9 showing a view of the internal structure of thecassette portion;

FIG. 12 is a graphical illustration of the heat extraction (power)capability of one embodiment of the present invention as a function ofprimary fluid temperature;

FIG. 13 is a graphical comparison of the temperature reducing capabilityof an embodiment of the present invention compared to the temperaturereducing capability of a prior system.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is primarily intended to include a catheter placedin the bloodstream of a patient for regulating the patient's bodytemperature, although those of skill in the art will understand thatvarious other applications for the system of the present invention arepossible. Indeed, the present invention may have applications beyondcontrolling the temperature of an internal body fluid, and the claimsshould not be so limited. In a preferred application, one or more of theheat exchange catheters of the present invention are positioned within apatient's vasculature to exchange heat with the blood in order toregulate the overall body temperature, or to regulate the temperature ofa localized region of the patient's body. Heat exchange fluid is thencirculated through the catheter to exchange heat between the blood andthe heat exchange fluid, and a controller manages the functioning of thesystem. The catheters may be, for example, suitable for exchanging heatwith arterial blood flowing toward the brain to cool the brain, and maythus prevent damage to brain tissue that might otherwise result from astroke or other injury, or cooling venous blood flowing toward the heartto cool the myocardium to prevent tissue injury that might otherwiseoccur following an MI or other similar event.

In general, the invention provides a preferred control unit and methodfor controlling the temperature and flow of heat transfer fluid for aheat transfer catheter used for controlling the body temperature of apatient. The control unit initially automatically supplies heat transferfluid to the heat transfer catheter to prime the heat exchange catheterfor use. It also receives input from the user, receives temperatureinformation from sensors that sense patient temperature information, andbased thereon, automatically controls the temperature and flow of theheat transfer fluid. Further, based on feedback from a pump in acassette containing the heat transfer fluid, the control unit suppliesheat transfer fluid at a relatively constant pressure. The cassette andthe controller, working together, have several warning or alarm statesthat alert the user of potentially hazardous situations, for example, byshutting down the pump motor and notifying the user if the fluid levelin the cassette is unacceptably low.

Overview of Heat Exchange System

Any suitable heat exchange catheter may be utilized in a heat exchangesystem for regulating the temperature of a patient or a region of thepatient's body and controlled by the control unit as disclosed herein.In addition to the catheters disclosed herein, and by way ofillustration and not of limitation, catheters that may be utilized inthis invention are the catheters disclosed in U.S. Pat. No. 5,486,208 toGinsburg, U.S. Pat. No. 5,837,003 to Ginsburg, U.S. Pat. No. 6,610,083to Keller et al., U.S. Pat. No. 6,702,840 to Keller et al., U.S. Pat.No. 6,752,786 to Callister, U.S. Pat. No. 6,620,188 to Ginsburg et al.,U.S. Pat. No. 6,849,083 to Ginsburg, U.S. Pat. No. 5,624,392 to Saab,and U.S. Pat. No. 6,440,158 to Saab, the complete disclosure of each ofwhich is hereby incorporated in full herein by reference. It will beunderstood by those skilled in the art that for the purposes ofproviding heat exchange with a patient at the rates possible using thevarious embodiments of the present invention, a catheter with sufficientheat exchange power must be employed.

While the various embodiments of the system and method of the presentinvention will be described with reference to providing a source ofcooling or heating fluid for circulation within a catheter, thoseskilled in the art will understand that the fluid may also be circulatedthrough other devices designed to alter the temperature of a patient.For example, instead of a catheter, the fluid may be circulated througha heating or cooling pad or blanket designed to be used externally to apatient.

One example of such a heat exchange catheter system 20 is shown in FIG.1, and includes a control unit 22 and a heat exchange catheter 24 formedwith at least one heat transfer section 44. The heat transfer section orsections are located on that portion of the catheter 24, as illustratedby section 26, that is inserted into the patient. This insertion portionis less than the full-length of the catheter and extends from thelocation on the catheter just inside the patient, when the catheter isfully inserted, to the distal end of the catheter. The control unit 22may include a fluid pump 28 for circulating a heat exchange fluid ormedium within the catheter 24, and a heat exchanger component forheating and/or cooling circulating fluids within the heat transfersystem 20. A reservoir or fluid bag 30 may be connected to the controlunit 22 to provide a source of heat transfer fluid such as, saline,blood substitute solution, or other biocompatible fluid. A circulatoryheat exchange flow channel within the catheter may be respectivelyconnected to inlet 32 and outlet 34 conduits of the pump 28 forcirculation of the heat transfer fluid through the balloon to cool theflow of body fluid such as blood within a selected body region. Asimilar arrangement may be implemented for heating of selected bodyregions simultaneously or independently of each other using the coolingcomponent of the system.

The control unit 22 may further receive data from a variety of sensorswhich may be, for example, solid-state thermocouples to provide feedbackfrom the catheter and various sensors to provide patient temperatureinformation representing core temperature or temperature of selectedorgans or portions of the body. For instance, sensors may include atemperature probe 36 for the brain or head region, a rectal temperatureprobe 38, an ear temperature probe 40, an esophageal temperature probe(not shown), a bladder temperature probe (not shown), and the like.Alternatively, a temperature probe may be placed in a patient's bloodvessel at a location adjacent the heat transfer balloon. In yet anotherembodiment, the temperature probe may be placed in the blood streamdistal of the heat transfer balloon.

Based upon sensed temperatures and conditions, the control unit 22 maydirect the heating or cooling of the catheter in response. The controlunit 22 may activate a heat exchanger at a first sensed temperature toheat fluid which is then circulated through the balloon, and may alsode-activate the heat exchanger at a second sensed temperature which maybe relatively higher or lower than the first sensed temperature or anyother predetermined temperature. Alternatively, the control unit mayactively cool the heat exchange fluid to cool the balloon. The controlunit 22 may operate multiple heat transfer units to independently heator cool different selected heat transfer sections to attain desired orpreselected temperatures in body regions. Likewise, the controller 22may activate more than one heat exchanger to control temperature atparticular regions of the patient's body. The controller might alsoactivate or de-activate other apparatus, for example external heatingblankets or the like, in response to sensed temperatures.

The regulation exercised over the heat transfer catheters or otherdevices may be a simple on-off control, or may be a significantly moresophisticated control scheme including regulating the degree of heatingor cooling, ramp rates of heating or cooling,proportional/integral/derivative (PID) or nonlinear control as thetemperature of the heat exchange region or patient approaches a targettemperature, or the like.

The control unit 22 may further include a thermoelectric cooler andheater (and associated flow conduits) that are selectively activated toperform both heating and cooling functions with the same or differentheat transfer mediums within the closed-loop catheter system. Forexample, a first heat transfer section 42 located on the insertionportion 26 of at least one temperature regulating catheter 24 maycirculate a cold solution in the immediate head region, oralternatively, within a carotid artery or other blood vessel leading tothe brain. The head temperature may be locally monitored withtemperature sensors 36 positioned in a relatively proximate exteriorsurface of the patient or within selected body regions. Another heattransfer section 44 of the catheter 24 also located on the insertionportion 26 may circulate a heated solution within a collapsible balloonor otherwise provide heat to other body locations through heat elementsor other mechanisms described in accordance with other aspects of theinvention. While heat exchange catheter 24 may provide regionalhypothermia to the brain region for neuroprotective benefits, otherparts of the body may be kept relatively warm so that adverse sideeffects such as discomfort, shivering, blood coagulopathies, immunedeficiencies, and the like, may be avoided or minimized. Warming of thebody generally below the neck may be further achieved by insulating orwrapping the lower body in a heating pad or blanket 46 while the headregion above the neck is cool. It should be understood of course thatmultiple heat exchange sections of the catheter 24 may be modified toprovide whole body cooling or warming to affect body core temperature.

Exemplary Heat Exchange System

The present invention contemplates the use of a re-usable controller orcontrol console having a heater/cooler device therein and which receivesa disposable heat exchange element coupled via conduits to a distalin-dwelling heat exchange catheter. More specifically, the controllerdesirably includes an outer housing having an opening or slot forreceiving the heat exchange element, the opening and housing ensuringreliable positioning of the heat exchange element in proximity with theheater/cooler device. In this manner, set up of the system isfacilitated because the operator only needs to fully insert and seat theheat exchange element into the controller opening in order to couple thereusable and disposable portions of the system.

In an exemplary embodiment, FIG. 2 illustrates a heat exchange cathetersystem that includes a re-usable control unit 50 and a plurality ofdisposable components including a heat exchange catheter 52, a heatexchange cassette 54, a saline bag 56, and a plurality of fluid flowconduits including a two-way conduit 74 extending distally from the heatexchange cassette 54. The re-usable control unit 50 includes an outerhousing 64 within which is provided a heater/cooler, a primary fluidcircuit reservoir, a primary fluid circuit pump, a controller processorand various control cables and temperature, pump and flow controls, allnot shown. Within control unit 50 is also a pump drive motor 68 whichdrives a secondary fluid circuit pump disposed within heat exchangecassette 54 through a solenoid driven engagement swing arm and coupling(not shown), an optical beam source 93 and optical beam sensor 94 whichmay be used to determine a fluid level within the heat exchange cassette54. In addition, a manual input unit (not shown) utilizing a graphicaluser interface enables an operator to enter desirable operatingparameters of the controller, for example a preselected temperature forthe brain. Each of the electronic devices provided within the controlunit 50 communicate through suitable wiring. The heat exchange cassette54 is in fluid communication with the primary fluid circuit throughprimary circuit fluid conduits or access points 67, 69, thus forming aclosed fluid circuit comprising the primary fluid circuit reservoir,primary fluid circuit pump and heat exchange cassette 54.

The heat exchange catheter 52 is formed with a catheter conduit 74 and aheat exchanger 76 which may be, for example, a heat exchange balloonoperated using a closed-loop flow of a biocompatible fluid that servesas the heat exchange medium. The catheter 52 may include a working lumen(not shown) for injection of drugs, fluoroscopic dye, or the like, andfor receipt of a guidewire 78 for use in placing the catheter at anappropriate location in the patient's body. A sensor 80 may be providedon the catheter 52 distal to the heat exchanger 76 to monitor thetemperature of the heat exchange balloon, and other sensors (not shown)may be provided as desired to monitor the blood temperature at thedistal tip of the catheter, at the proximal tip of the balloon, or atany other desired location along the catheter.

The heat exchange cassette 54 includes a heat exchanger 96 and a fluidreservoir compartment that houses a secondary fluid circuit pump. In apreferred embodiment, the secondary fluid circuit is a closed systemphysically isolated from the primary fluid circuit by heat exchanger 96but with the secondary fluid circuit and the primary fluid circuit inheat exchange communication through the heat exchanger. This arrangementis advantageous in that different fluids may be used in the primaryfluid circuit that are not necessarily biocompatible so as to maximizethe efficiency of the heat exchanger 96 during heating or cooling of apatient.

As seen in FIG. 2, the proximal end of the catheter conduit 74 may beconnected to a multi-arm adapter 82 for providing separate access tovarious channels in the catheter 52. For example, a first arm 84 mayprovide access to the working lumen of the catheter 52 for insertion ofthe guidewire 78 to steer the heat exchange catheter to the desiredlocation. First arm 84 may also be used to provide access to the bloodstream for a temperature probe to monitor the blood temperature forcontrol input.

Where the heat exchanger 76 is a heat exchange balloon for closed-loopflow of secondary fluid, the adapter 82 may contain a second arm 86connected to an inflow line 88, and a third arm 90 connected to anoutflow line 92. The inflow line 88 and outflow line 92 are thereforeplaced in flow communication with respective inflow and outflow channels(not shown) provided in the conduit 74 and heat exchanger 96. In thisregard, the inflow and outflow lines 88, 92 may come together to formthe dual channel conduit 62 connected to the heat exchange cassette 54.

A vent tube 61 including a valve 63 may be used to assist in priming thesecondary fluid circuit. Furthermore, an external biocompatible fluidsource such as the saline bag 56 may be placed in fluid communicationwith the secondary fluid circuit using suitable connecters. As will beexplained further below, the external fluid source 56 is used to primethe secondary fluid circuit, including the closed-loop heat exchangeballoon system.

Still with reference to FIG. 2, and as described above, the heatexchange cassette 54 depicted in this embodiment desirably includes theheat exchanger 96 and a fluid reservoir compartment 98, which also holdsthe secondary fluid pump. The secondary fluid circuit pump in thereservoir compartment 98 pumps heat exchange fluid through the secondaryfluid circuit through the heat exchanger 96, and through the associatedconduits and catheter 52. As mentioned, the heat exchange cassette 54 isconfigured to install into the control unit 50. In this regard, the heatexchange cassette 54 is desirably sized to fit through an elongate slot102 in the control unit housing 64. Once inserted, the cassette 54 isplaced in proximity to and engaged with the pump drive motor 68. Theheat exchanger 96 is connected to the primary fluid circuit using inflowand outflow conduits, or access points, 67, 69.

When the heat exchanger cassette 54 is properly installed in the controlunit 50, the heater/cooler may act to heat or cool the primary heatexchange fluid as that fluid is circulated through in heat exchangecontact with the secondary fluid in heat exchanger 96. The secondaryfluid, which is either being heated, cooled or maintained by the heatexchange contact with the primary fluid in the heat exchanger 96, ispumped through the conduits leading to the in-dwelling heat exchanger76. When the heat exchange fluid is circulated through the heatexchanger 76 located in the patient's body, it may act to add or removeheat from the body. In this way, the control unit 50 regulates the bloodtemperature of the patient as desired.

A solid-state thermoelectric heater/cooler may be used to heat or coolthe primary circuit fluid, and such use is advantageous because the sameunit is capable of either generating heat or removing heat by simplychanging the polarity of the current activating the unit. Therefore, theheater/cooler may be conveniently controlled so as to supply or removeheat from the system without the need for two separate units and withoutexchange of the heat exchange cassette or catheter. In anotherembodiment, a variable speed vapor compressor/heat pump could also beused as the heater/cooler. Alternatively, a resistive heater could beused in combination with a variable or constant speed compressivecooler.

The heater/cooler and the pump drive motor 68 are responsive to thecontroller processor, which receives data input through electricalconnections to numerous sensors, for example body temperature sensorspositioned to sense the temperature at various locations within thepatient. For example, the temperature may be sensed at the patient'sear, brain region, bladder, rectum, esophagus, or other appropriatelocation as desired by the operator. Also, as mentioned, a sensor 80 maymonitor the temperature at a location distal of the heat exchanger 76,and other sensors along the catheter 52 may provide input to thecontroller processor. Additionally, the manual input unit allows anoperator to provide operating parameters to the control system such as,for example, a pre-selected temperature for the brain and/or the wholebody of the patient. The operator input parameters are communicated tothe controller processor by means of appropriate wiring.

The controller processor coordinates the various data received andselectively actuates the several operational subsystems to achieve andmaintain desired results; i.e., proper regulation of the patient's bodytemperature. For example, the processor may actuate the heater/cooler toincrease the amount of heat it is removing if the actual temperature isabove the specified temperature, or it may decrease the amount of heatbeing removed if the temperature is below the specified temperature.Alternatively, the processor may slow or stop the pumping of the primaryor secondary, or both, heat exchange fluids when the sensed body orregional temperature reaches the desired temperature.

In operation, the heater/cooler warms or chills the fluid in the primaryfluid circuit in response to temperature signals received from thetemperature sensors described above to alter the temperature of thepatient's body, or a portion of the patient's body, as desired. Thechanges in temperature of the primary fluid circuit is transferred tothe fluid circulating in the secondary fluid circuit using the heatexchanger 96, in a manner that is well known to those skilled in theart. Thus, the heater/cooler is used to indirectly affect thetemperature of the patient, or a portion of the patient by heating orcooling the fluid circulating in the secondary fluid circuit.

Referring still to FIG. 2, the heat exchange cassette 54 of thisembodiment is shown as being attached to a heat exchange catheter 52,external fluid source 56 is positioned in cooperation with a suitablereusable control unit 50. Prior to commencing treatment, theheat-exchange unit 54 is inserted into the reusable control unit 50, theexternal fluid source 56 is attached to the fill port and the pump 68 isautomatically or passively primed and the disposable system filled,after which the catheter is ready for insertion in-the vasculature ofthe patient, for example in the inferior vena cava or the carotidartery. Chilled or warmed biocompatible fluid such as, for example,saline filling the secondary circuit, is pumped into the closed circuitcatheter, which exchanges heat directly with the patient's blood. Thecontrol unit serves to automatically-control the patient's temperature.Once treatment with the catheter is complete, the catheter is removedfrom the patient and the cassette is removed from the reusable controlunit. Both the catheter and cassette may then be discarded. The reusablecontrol unit, however, which never comes into direct contact with thesecondary heat exchange fluid, is ready for immediate use for treatmenton other patients, along with a new cassette and catheter and freshexternal fluid source. Alternatively, the heat exchanger 96 may beseparated from the cassette 54, cleaned and sterilized, while thecassette is discarded. In yet a further alternative, the entire heatexchange cassette 54 may be suitably reconditioned for use with anotherpatient.

Exemplary Method of Temperature Control

The flowchart seen in FIGS. 3A and 3B illustrates an exemplary sequenceof steps that the controller processor of the system coordinates duringtemperature regulation of a patient. First, in step 110, a targettemperature for the target tissue (which may be the entire body) isselected, generally by user input. The target temperature may bedifferent than the body temperature, or may be the same if maintenanceof normal patient temperature is the goal. Steps 112 a and 112 b involvedetermination of an upper variance set point and a lower variance setpoint, respectively. This is generally a pre-set buffer range above andbelow the target temperature that is built or programmed into thecontroller processor. These variance set points straddle the targettemperature and create a buffer range of temperature within which thecontroller operates.

More specifically, the sensed temperature for the target tissue isobtained in step 114 prior to or after step 116 in which a heatexchanger capable of either heating or cooling body fluid is placed inproximity with body fluid that subsequently flows to the target tissue.Based on user input, or on a comparison between the target temperatureand the sensed tissue temperature, a determination is made in step 118as to whether the heat exchanger will be operating a cooling mode, aheat mode, or a maintaining mode. That is, if the target temperatureequals the tissue temperature then there will be no need to initiallyheat or cool the body fluid and the control unit will control the heatexchanger to maintain the tissue or blood temperature at the targettemperature.

The determination step 118 leads to three different modes of operationof the system, depending on whether the system will be COOLING, HEATING,or OFF. These modes of operation correspond to steps 120 a, 120 b, and120 c, which appear on both the FIGS. 3A and 3B.

If the system is in the COOLING mode, the flowchart logic leads to step120 a which compares the sensed tissue temperature with the pre-selectedtarget temperature. If the tissue temperature is greater than the targettemperature, the system continues cooling as indicated in step 122, andthe processor returns to decision step 118. On the other hand, if thesensed tissue temperature is equal to or less than the targettemperature, the heat exchanger is converted to the OFF mode asindicated in step 124 and the processor returns to decision step 118.

If the system is in the HEATING mode, the flowchart logic leads to step120 b which also compares the sensed tissue temperature with thepre-selected target temperature. If the tissue temperature is less thanthe target temperature, the system continues heating as indicated instep 126, and the processor returns to decision step 118. On the otherhand, if the tissue temperature is equal to or greater than the targettemperature, the heat exchanger is converted to the OFF mode asindicated in step 128, and the processor returns to decision step 118.

If the system is in the OFF mode, the flowchart logic leads to step 120c which compares the sensed tissue temperature with the upper variancetemperature set point. Then, if the sensed tissue temperature is equalto or greater than the upper variance set point, the system is convertedto the COOLING mode as indicated in step 130, and the processor returnsto decision step 118. If the tissue temperature is less than the uppervariance set point, the processor continues to step 132 in the flowchartlogic, and determines if the tissue temperature is equal to or less thanthe lower variance set point, whereby the system is converted to theHEATING mode and processor returns to decision step 118. Finally, if thetissue temperature is between the upper and lower variance set points,the system does nothing as indicated in step 134, and the processorreturns to decision step 118.

FIG. 4 is a graphical illustration plotting the fluctuating sensedtissue temperature over a period of time relative to the targettemperature and variance set points. In the example, the targettemperature is set at 31 degrees Celsius, with the upper and lowervariance set points ½ degrees on either side. Initially, the sensedtissue temperature is greater than the target temperature, such as ifthe heat exchange catheter is placed in contact with blood at 37 degreesCelsius. The system is first placed in the COOLING mode so that thesensed tissue temperature is reduced until it equals the targettemperature at 136, corresponding to steps 120 a and 124 in FIG. 3A. Instep 124, the heat exchanger is converted to the OFF mode, which resultsin the sensed tissue temperature climbing until it reaches the uppervariance set point at 138, corresponding to step 130 in FIG. 3B, atwhich time the system begins cooling again. This cycle is repeated inthe region indicated at A.

Eventually, the patient may be unable to maintain even the targettemperature as shown by the temperature profile in the region indicatedat B. For example, after the sensed tissue temperature reaches thetarget temperature at 140, and the heat exchanger is turned OFF, thesensed target temperature may continue to drift lower until it reachesthe lower variance set point at 142. The controller logic senses this instep 132 of FIG. 3B, and converts the system to the HEATING mode.Subsequently, the sensed tissue temperature climbs to the targettemperature at 144, and the system is again turned OFF, corresponding tosteps 120 b and 128 in FIG. 3B. Alternatively, depending on the patientand the situation, it may be that after the sensed tissue temperaturereaches the target temperature and the heat exchanger is turned OFF, thepatient's temperature may begin to increase until it rises to the uppervariance set point temperature, at which point, as described in box 130the heat exchanger begins to COOL. As can be appreciated, the sensedtissue temperature continues to fluctuate between the upper and lowervariance set points in this manner.

The control scheme as applied to the system of the present invention hasthe advantage of allowing the operator to essentially input a desiredtemperature after which time the system will automatically regulate thetissue temperature until it reaches the target temperature, and willmaintain the tissue temperature at that target temperature. The bufferrange created by the upper and lower variance set points prevents thecontroller from turning the heater/cooler on and off or activating andde-activating the primary or secondary pumps in rapid succession,actions that would be potentially damaging to these electric devices.Moreover, the variance points, and other parameters used by thecontroller to regulate the cooling or heating power of the heater/coolercan be varied by the operator during the course of treatment to changethe selected patient temperature or the ramp of the heating or coolingas needed to address specific therapeutic situations. A moresophisticated control scheme, such as the PID scheme described below,may also be employed.

Exemplary Control Unit

FIGS. 5A-5C are various views of an exemplary heat exchange control unit150 of the present invention that is particularly suited for rapidtemperature regulation of a patient.

As seen in the Figures, the control unit 150 comprises avertically-oriented outer housing having a lower portion 152 and upperportion 154 separated at a generally horizontal dividing line 156located close to the top of the unit. The control unit 150 is mounted onwheels 158 for ease of portability, with the wheels preferably being ofthe swivel type having foot-actuated locks. For ease of servicing, theupper and lower portions may be joined together with hinges 155 at theback so that the top portion may be lifted up and rotated back to exposethe interior of the unit. In an exemplary embodiment, the control unit150 has a height that enables an operator to easily access an uppercontrol panel 160 without the need for significant bending. For example,the control unit 150 may have a total height of between approximately2-3 feet, and preferably about 32 inches. The substantially horizontalcross-section of a majority of the control unit 150 may have widths ofbetween one and two feet, although the lower portion 152 preferablywidens at its lower end with the wheels 158 mounted on the lower cornersto provide greater stability.

FIG. 5A illustrates the front and right sides of the unit 150 whereinthe control panel 160 is visible on an angled upper panel 162 of theupper portion 154 front side. The angled upper panel 162 also defines afluid container receiving cavity 164 adjacent the control panel 160.Further, a plurality of handles 166 may be provided to help maneuver thecontrol unit 150.

A heat exchange cassette-receiving opening 168 is also provided on afront panel 169 of the control unit 150, just below the horizontaldividing line 156. As will be explained below, the opening 168 is sizedand shaped to receive a cassette of the present invention, analogous tothe heat exchange cassette-receiving opening 102 shown in FIG. 2.Likewise, the control unit 150 provides all of the features that weredescribed above for the control unit 50 of FIG. 2, including equipmentfor heating or cooling the fluid in the cassette, a pump driver, acontroller processor/microprocessor, and a manual input unit, namely thecontrol panel 160.

Also shown in FIG. 5A are access points 165, 167. These access pointsare used to fluidly connect the heat exchanger to the primary fluidcircuit. Access points may be configured as flexible tubing which isterminated by quick connect couplings that allow for rapid attachmentand detachment of the access points from the cassette. The couplings mayalso be configured to seal upon disconnect, thus preventing loss ofprimary fluid from the primary fluid circuit. Additionally, thecorresponding quick connect couplings disposed on the cassette may alsobe configured to prevent loss of primary fluid from the primary fluidside of heat exchanger in the cassette when the access points aredetached. Alternatively, the quick connect couplings may be configuredsuch that insertion of the cassette into the slot 168 causes quickconnect fittings disposed on the cassette to automatically engage andfluidly couple with quick connect fittings within the housing tocomplete the fluid pathway of the primary fluid circuit so that primaryfluid may be circulated through the primary fluid side of the heatexchanger in the cassette.

Because of the relatively high capacity for heating and cooling, thelower portion 152 of the control unit housing includes a plurality ofvents 170 to facilitate convective heat exchange between the interior ofthe housing and the surrounding environment and to direct vented airaway from the user or patient. The control unit housing may bemanufactured of a number of suitably strong and corrosion-resistantmaterials, including stainless-steel, aluminum, or molded plastic.Desirably, the components of the control unit 150 are adapted to run onconventional power from a catheterization lab power outlet, for example.

The present invention also contemplates the use of two different controlunits in sequence, depending on need. For example, the control unit 150of FIGS. 5A-5C having a relatively large heat transfer capacity andlarge housing can be used initially to rapidly alter the patient's bodytemperature. Subsequently, a smaller unit having an internal batterypower source can be substituted for convenience and economy. Both thelarge and small control units desirably define the same sized andconfigured cavity for receiving a cassette of the present invention. Inthis manner, the cassette may be de-coupled from one unit, the patienttransported with the cassette in place to another location without thefirst unit, and the cassette coupled to another unit for a subsequentoperation/therapy. The present invention also encompasses a situationwherein the cassette is de-coupled from a first unit and then coupled toa second unit of the same size. This simply obviates the need totransport control units with the patient.

Exemplary Control Panel

FIGS. 5B and 5C illustrate in greater detail the upper portion 154 ofthe control unit 150, and in particular the control panel 160. FIG. 5Bshows a facade 172 exploded from the control panel 160, with the facadeshown in FIG. 5C having indicia printed thereon corresponding to variousdisplays and buttons. (The reader will notice that the control panel 160in FIG. 5C is an alternative embodiment from one shown in otherdrawings, and includes several added features and with several buttonsand/or displays being slightly relocated). The following is adescription of the physical characteristics of the control panel 160,with a description of an exemplary method of using the control panel tofollow later in the description.

The exemplary control panel 160 of FIG. 5C provides a number of visualdisplays, including, from top to bottom along the centerline, a patienttemperature display 174, a target temperature display 176, acooling/warming rate display 178, and a system feedback/status display180. Other desirable information may be displayed, either with anadditional display, or alternating with information displayed on one ofthe screens shown here, or by user initiated request from one of thescreens shown here. For example, by way of illustration but notlimitation, if the ramp rate for heating or cooling the patient is setby the user, or is calculated by a control microprocessor, or theprojected time to target temperature is calculated, those values may beshown. The larger displays for alphanumeric characters are preferablyliquid crystal displays (LCD), while several light emitting diode (LED)status indicators are also provided. Several graphic icons arepositioned adjacent the left of the upper three LCD displays 174,176,and 178, to indicate their respective display functions. Specifically, apatient temperature icon 182 a, a target temperature LED 182 b, and acooling/warming rate LED 182 c are provided. Just below thecooling/warming rate LED 182 c, an operational mode LED 182 d andassociated vertical series of three mode indicators 184 are provided.Only one of the indicators 184 lights up at any one time, depending onwhether the system is in the COOLING, WARMING, or MAINTAINING mode. Inlieu of the mode indicators 184, the display 180 may carry the messageCOOLING PATIENT, WARMING PATIENT, or MAINTAINING so that the operatorcan easily identify the mode of functioning of the controller. Therealso may be only one patient temperature icon 182 which has a line oflights that streams upward if the unit is warming, downward if the unitis cooling, and blinks stationary if the unit is maintaining. Finally, apower on/off indicator LED is provided in the lower left corner of thecontrol panel 160.

The control panel 160 also exhibits a number of input buttons including,in descending order on the right side of the control panel, aCelsius/Fahrenheit display toggle 190, a pair of target temperatureadjustment buttons 192, a pair of cooling/warming rate adjustmentbuttons 194, a multi-function/enter button 196, and a mute audible alarmbutton 198. The mute audible alarm button 198 is nested within an LEDalarm indicator 200. Finally, in the lower central portion of thecontrol panel 160, a stop system operation button 202 permits instantshutdown of the system.

With reference again to FIGS. 5A and 5B, the housing includes a cassettereceiver 168 which includes an internal cavity 242 into which a heatexchange cassette of the present invention can be inserted. In thepreferred embodiment, a cassette is provided as described in greaterdetail below comprising a reservoir portion which is in fluidcommunication with a heat exchanger. Although not shown, a micro-switchis desirably provided in the slot 168 mounted on one of the walls of thecassette receiver cavity to indicate when the heat exchange cassette hasbeen fully inserted into the internal cavity 242, and is engaged thereinfor proper operation of the system. Also not shown but well known in therelevant art, registration means such as pressure pins or balls andmating detents may be provided in the control unit and cassetterespectively to aid in the correct relative positioning between thecassette and the control unit. This arrangement also provides, in someembodiments, for simultaneous engagement of the motor and fluidconnections to the cassette, providing for easy insertion and setup ofthe cassette.

Referring now to FIG. 6, the primary and secondary cooling circuitsutilized by a preferred embodiment of the present invention will now bedescribed. In the embodiment shown, a primary fluid circuit 215comprises a pump 217 that draws primary circuit fluid from a primarycircuit reservoir 219. The primary circuit fluid is pumped underpressure through line 218 through a primary circuit heat exchanger 221.As described above, primary circuit heat exchanger may include aheater/cooler, such as thermoelectric heater/cooler for heating orcooling the primary circuit fluid. A blower 223 may be included toassist in removal of excess heat generated by the heater/cooler or toprovide the thermal gradients required for proper operation of theheater/cooler. Alternatively, other means for heating or cooling theprimary circuit fluid may be used, such as a water bath that can beheated or cooled as desired, or by using a suitable compressor operatinga refrigeration cycle that is familiar to those skilled in the art. Forexample, use of refrigeration to cool the primary fluid would requiresome way to warm the primary fluid, such as, for example, a heat pump,resistive heating, radio frequency (RF), microwave or other suitableheating method. Similarly, cooling of the primary circuit can beprovided by an ice bath, or other suitable stored energy source such ascompressed or liquefied gas, or endothermic reactive chemicals. Theprimary fluid circuit may be any suitable fluid or gas, and is notrequired to be bio-compatible. In other instances, the primary fluidcircuit may be bio-compatible, such as for example, saline. The fluidmay also be a suitable slurry, such as slush of brine or other fluid.

The temperature of the fluid circulating within the primary fluidcircuit line downstream of the heat exchanger 221 is sensed using asuitable temperature sensor, such as, for example, a thermocouple orthermistor 224, 273, that provide temperature signals to, for example, athermoelectric controller 235. Alternatively, the temperature signalsmay be sent to system controller 237. Those skilled in the art willunderstand that the function of thermoelectric controller 235 may beincluded in the functions carried out by system controller 237, and thusthe scope of the invention does not require a separate thermoelectriccontroller.

In this embodiment, temperature sensor 273 monitors the temperature ofthe primary fluid returning to the reservoir 219. The signals from thissensor may be used to continuously monitor and calculate the cooling orheating power being delivered. The power may be calculated because theinlet temperature to the heat exchanger 229 is measured by temperaturesensor 224, and the pump speed, and thus the speed of flow through theheat exchanger, is also known. The calculation of power from thesevalues is well known by those skilled in the art. Monitoring the poweris useful because a change in power may indicate a problem, either inthe primary loop or the secondary cooling loop. For example, should theprimary fluid circuit experience a drop in fluid flow or a decrease inheat exchange, the temperature of the primary circuit sensed attemperature sensor 224 would decrease when cooling, or rise whenheating. Upon receiving the temperature signal from sensor 224, thecontroller may cause a variety of actions to occur to ensure the safetyof the patient. For example, the controller may stop the pump and causean alarm to be sounded.

In the depicted embodiment, the primary fluid circuit 215 includes avalve 225 and a valve 227 to control the path the fluid circulatingwithin the primary fluid takes. In this embodiment, valve 225 is asolenoid valve that is normally closed, and valve 227 is a solenoidvalve that is normally open. Both valves 225 and 227 are controlled bysignals from controller 237. In this arrangement, fluid exiting theprimary heat exchanger 221 is diverted by valve 225 into cut off line226, where normally open valve 227 provides an open pathway for thecirculating fluid to return to primary fluid reservoir 219 through line239. In this manner, the present invention provides a closed loop thatallows for continuous pumping of primary circuit fluid through primaryheat exchanger 221 and into primary fluid circuit reservoir 219 whenheat exchanger 229 is not connected to the system, allowing thetemperature of the primary fluid circuit 215 to be heated or cooled asdesired, and then maintained at a temperature, ready to provide a largestored amount of heating or cooling when the operator controls thesystem to beginning heating or cooling the blood of the patient. Theadvantages of such a system will be discussed in more detail below.

The interface between primary fluid circuit 215 and secondary fluidcircuit 255 is provided by heat exchanger 229. As shown, heat exchanger229 provides the means to transfer heat energy, either in heating orcooling mode, between the primary and secondary fluid circuits 215 and255.

Heat exchanger 229 includes a pair of fluid pathways, which be thoughtof as intermediate fluid pathways. These two intermediate pathways, aprimary intermediate pathway and a secondary intermediate fluid pathway,are physically separated from each other, but are in thermalcommunication with each other. This provides for the exchange of heatenergy between the intermediate fluid pathways, while preventing thepossibility of contaminating the secondary heat exchange fluid which mayflow into a patient with primary fluid circuit fluid, which may or maynot be biocompatible. Similarly, the physical separation of the primaryand secondary intermediate fluid pathways prevent the contamination ofthe primary fluid circuit should blood or other bodily fluids invade thesecondary fluid circuit.

These intermediate fluid pathways, when connected to their respectiveprimary or secondary fluid circuits, increase the volume of thesecircuits. This provides several advantages that will be discussed inmore detail below.

Secondary fluid circuit 255 comprises a cassette 257 that includes heatexchanger 229, a secondary fluid circuit reservoir 259 and secondaryfluid circuit pump 261. Fluid contained within secondary fluid circuit255 is drawn from reservoir 259 by pump 261 and forced down supply line265 to a heat exchanger 263, such as a balloon mounted on a distal endof a catheter, as described previously, that has been positioned withina patient's blood vessels. After the secondary fluid has passed throughheat exchanger 263, the fluid flows through return line 267 to heatexchanger 229 and then back into reservoir 259 to complete the closedloop of the secondary fluid circuit 255. In an alternative embodiment,the order of heat exchanger 263 and heat exchanger 229 are reversed sopump 261 forces fluid through the secondary side of heat exchanger 229and then down supply line 265, and return line 267 empties intoreservoir 259. A separate fluid supply 269, such as a bag of saline, mayalso be in fluid communication with the secondary fluid circuit throughappropriate lines and valves to provide a source for additionalsecondary fluid should for priming the secondary fluid circuit or tomake up any secondary fluid that is inadvertently lost during treatmentof a patient. Fluid supply 269 and reservoir 259 provide compliance forthe secondary fluid circuit to accommodate volume changes in the fluidcircuit due to heating and cooling of the fluid circuit. Similarly, theprimary fluid tank 219 provides compliance for the primary fluidcircuit.

The temperature of the secondary fluid circulating through the secondaryfluid circuit may be measured using temperature sensors, such as sensors270, 271, whose signals are communicated to controller 237. These, andother signals, may then be used by controller 237 to control the heatingand cooling of the patient by controlling the heating and cooling of theprimary fluid circuit or to provide an alarm or take other action shouldthe values of the signals sensed by sensors 270, 271 indicate that thedevice is not functioning properly. Additionally, controller 237 maycontrol the speed of pump 261 independently, or in conjunction withcontrolling heat exchanger 221, to heat or cool the patient to a desiredtemperature at a desired rate of temperature change.

The primary fluid circuit side of heat exchanger 229 is removablyconnected to the primary fluid circuit using quick connect/shutoffvalves 231, 233. Use of these quick connects allows the heat exchanger229 to be removed from the primary fluid circuit without a substantialloss of primary fluid circuit fluid. Additionally, primary circuit fluidwill not flow into heat exchanger 229 unless controller 237 provides avalve open signal to normally closed valve 225. As will be apparent tothose skilled in the art, when the controller 237 provides a valve opensignal to normally closed valve 225, controller 237 also provides avalve closed signal to normally open valve 227 located in cutoff line226 to close off cutoff line 226 from the primary fluid circuit,ensuring that all primary fluid circuit is directed through heatexchanger 229.

As noted above, this arrangement is advantageous as it provides forcontinuous circulation of primary fluid within primary fluid circuit215, which allows the temperature of the primary fluid circuit 215 to beheated or cooled to a desired temperature, and then held at thattemperature, even if a patient is not being treated at the time. This isparticularly advantageous where a patient requires rapid heating orcooling. In some prior art systems, the cooling media used to cool thepatient by necessity was a room temperature at the beginning oftreatment. Thus, the rate of cooling or heating of the patient wasdependent on the ability of the system to add heat to or remove heatfrom the cooling media. This could be problematic in the event rapidcooling of the patient was desirable, since in many cases the system wasnot capable of removing heat from the patient's blood at a ratesufficient to achieve the desired cooling rate.

The system of the present invention addresses this need by providing areservoir of already cooled (or heated, depending on the needs of theemergency) primary circuit fluid. Since the primary fluid is alreadycooled, the rate of cooling no longer depends solely on the coolingcapacity of heater/cooler 221, but rather on the combined coolingcapacity of the pre-cooled fluid and heater/cooler 221. In effect, thisembodiment of the present invention provides what the inventor hasidentified as a “turbo boost” in the heating/cooling capacity of thesystem that is helpful where a patient needs to be rapidly cooled orwarmed to provide an enhanced therapeutic effect. The relative amount of“turbo boost” can be adjusted by adjusting the temperature of theprimary fluid in the primary fluid reservoir, or by increasing the sizeof primary fluid reservoir 219, or both.

In an alternative embodiment, the supply line 265 and the return line267 may include couplers, such as luer lock fittings 275, 277. Such anarrangement is advantageous in that it allows the cassette to bedisconnected from the catheter 263 during treatment of the patient, ifnecessary. In another embodiment, the heat exchanger may includeconnections for connecting a sensor line from sensors associated withthe catheter such that the sensor line is connected to the commandprocessor at or about the same time that the access points areconnected, thus facilitating rapid set up of the system.

In yet another alternative embodiment, the access points in the primaryfluid circuit allow the primary fluid reservoir to be easily filled withprimary fluid. Additionally, the access points allow for draining theprimary fluid reservoir of primary fluid to facilitate replacement ofthe reservoir, shipment of the device as otherwise deemed necessary forconvenience or safety.

In still another embodiment, the primary fluid circuit may include ameans for ensuring that the electrical resistivity of the primary fluidremains above a predetermined threshold to ensure the electricalisolation of the primary fluid circuit and the safety of the patient.One means for accomplishing this is to include a de-ionizing cartridge282 containing a suitable ion-exchange resin in the primary fluidcircuit. The flow through the de-ionizing cartridge may be controlled toallow the entirety of the fluid circulating in the primary fluid circuitto flow through cartridge 282, or it may be controlled to treat only aportion of the fluid returning through the primary loop into the tank219.

In yet another embodiment, the access points allow the heat exchanger tobe easily and rapidly disconnected from the primary fluid circuit in theevent of a power failure or other problem. In this manner, analternative method of providing primary fluid can be used, such as, forexample, circulating ice water through the primary fluid side of theheat exchange using a system suitable configured to do so.

To protect the primary fluid circuit 215 and pump 217 against overloadswhere valves 225 and 227 are both closed, an internal bypass loop 284may be disposed in the primary fluid circuit. Bypass loop 284 mayinclude a check valve 286 which is set to open a predetermined pressurethat is low enough to prevent damage to the pump. The inclusion of thebypass loop is also advantageous in that any blockage of the heatexchanger 229 or inadvertent disconnection of quick couplings 231 or233, that results in increased primary circuit pressures which maydamage the heat exchanger 229 may also be relieved by setting theopening pressure of check valve 286 at an appropriate level.

An active or passive vent valve 280 may also be included in thesecondary fluid circuit. Inclusion of this valve is useful in ventingair from the secondary fluid circuit to assist in priming the secondarycircuit with secondary circuit fluid prior to use of the cassette.

In an alternative embodiment, monitoring and controlling the performanceof the system may be carried out by monitoring the temperature in theprimary fluid circuit only. Monitoring the temperature of the primarycircuit provides information to the controller that may be used tocalculate the amount of heat energy that needs to be added to orsubtracted from the primary fluid circuit so as to drive the heatexchange ability of the secondary fluid circuit to alter the temperatureof the patient's tissue or blood.

FIG. 7 depicts an alternative embodiment of the system of the presentinvention. In this embodiment, the flow through primary fluid circuit310 and secondary fluid circuit 312 are altered. As depicted, primaryfluid circuit pump 217 now draws fluid through heat exchanger 229 ratherthan pumping fluid through it as shown in FIG. 6. Moreover, normallyclosed valve 225 is located between reservoir 219 and heat exchanger229. Thus, heat exchanger 229 is located on the negative pressure sideof pump 217. Similarly, secondary fluid flow through heat exchanger 229is reversed, necessitated by the change in flow direction of the primaryfluid circuit. An active or passive vent valve 313, vent line 314 andvent filter 315 are also in fluid communication with the primary fluidcircuit on the negative pressure side of pump 217.

There are several advantages of this arrangement. One inconvenienceposed by using a removable heat exchanger 229 is the need to empty theheat exchanger 229 of primary circuit fluid when the heat exchanger 229is detached from the primary fluid circuit. This arrangement addressesthat inconvenience by allowing pump 217 to empty heat exchanger 229 ofprimary circuit fluid before the heat exchanger is detached. Forexample, when the heat exchanger is to be detached after providingtreatment to a patient, an operator, using the manual input unit (FIG.5), can direct the controller 237 to send a valve close signal to valves225 and 227 and a valve open signal to vent valve 313. This effectivelycloses off the supply of primary fluid from the reservoir feeding pump217, but opens a path to the air through vent valve 313, vent line 314and vent filter 315. This allows the pump to suck the primary fluid fromheat exchanger 229 and pump the fluid into reservoir 219 for storage.When the primary side of heat exchanger 229 has been exhausted ofprimary fluid, the controller 237, either automatically having sensedthat the fluid is exhausted, or after receiving a manual command fromthe operator, sends a valve close signal to vent valve 313 and a valveopen signal to valve 227 to close off the vent line and restore fluidflow through cutoff line 226. It will be understood that while the abovehas been described with reference to various valve open and valve closesignals, where normally open or normally closed valves are used, nosignal will be necessary to place the valves in their normal state.Rather, the controller may simply stop providing a signal that placesthe valve in an other than normal state. In an alternative embodiment,the vent valve could be in communication with the inlet side of the pump217 in FIG. 6. Such an arrangement would require an additional valve.However, this arrangement, while workable, is not preferable.

A further advantage to the embodiment of the present invention depictedin FIG. 7 is that placing heat exchanger 229 on the negative pressureside of the pump facilitates keeping the secondary primary circuit at anincreased pressure relative to the pressure of the primary fluidcircuit, which enhances the safety of the system should a leak developin the primary fluid circuit of heat exchanger 229 by preventingencroachment of the primary fluid into the secondary fluid circuit.Alternatively, the secondary circuit could be controlled so as to have ahigher pressure than the primary circuit by having the pump pushsecondary fluid through the heat exchanger 229 and then through thecatheter.

Exemplary Electronic Control Circuit

As an alternative to the control system described in conjunction withFIGS. 3A-3B and the graph of FIG. 4, the controller may employ acascading PID control scheme. In such a scheme, a control system isprovided that may be divided into two sections: (a) a Bulk PID controlsection which takes input from the user (in the embodiment shown, RAMPRATE and TARGET TEMPERATURE) and input from the sensors on the patientrepresenting patient temperature, and calculates an intermediate setpoint temperature (SPI) and an output signal to the primary fluid PIDcontrol; and (b) the primary fluid PID control, that receives input fromthe bulk PID control section and from a sensor representing thetemperature of the primary fluid, and generates a signal that controlsthe temperature of the TE cooler by varying the power input to the TEcooler. The primary fluid circulates in heat transfer proximity to theTE cooler, so the primary fluid PID essentially controls the temperatureof the primary fluid. In this way, the control scheme is able toautomatically achieve a specified target temperature at a specified RAMPRATE based on input from sensors placed on the patient and the logicbuilt into the controller. Additionally, this scheme allows the unit toautomatically alter the patient temperature very gradually the last fewtenths of a degree to achieve the target temperature very gently andavoid overshoot or dramatic and potentially damaging swings in theelectronic power to the TE cooler. Once the target temperature isachieved, the system continues to operate automatically to add or removeheat at precisely the rate necessary to maintain the patient at thetarget temperature.

Specifically, this is achieved as illustrated in FIG. 8. FIG. 8illustrates an exemplary control schematic of components of the presentinvention specifically adapted for use in control unit 150 of FIG. 5A,but applicable to any control unit described herein. Some of theseelements correspond to elements identified previously, and thus, whereappropriate, reference numbers will be repeated for clarity. In general,the control circuit includes a control board having a number of logicalcomponents indicated within the dashed line 322, a user input 324, adisplay output 326, a plurality of sensors 328, a number of elements ofelectronic hardware indicated within the box 330, and a safety system332. The user inputs 324 and display outputs 326 were described abovewith respect to the control panel 160 of FIG. 5C. The two user inputs324 applicable to the control circuit in this embodiment are the targettemperature adjustment buttons 192 and cooling/warming rate adjustmentbuttons 194. The display outputs 326 applicable to the control circuitare the patient temperature display 174 and the alarm display 200, butmay include a number of other displays for various feedback to the user.A plurality of sensors 328 may be provided, including at least a sensor327 that senses the patient's actual body temperature and generates asignal represented by line 326, and a sensor 329 that directly orindirectly senses the temperature of the primary fluid and generates arepresentative signal 331.

After the system is primed, a set point temperature (SP1) is determinedwith a set point calculator 334 using the target temperature and thedesire ramp rate as inputs. This set point temperature represents aninterim target temperature that the system will achieve at any giventime, for example 0.1° C. each 6 minutes, if the ramp rate is 1° C. perhour, starting with the initial patient temperature. This set pointtemperature is transmitted to a Bulk PID control section 336 of thecontrol board. The Bulk PID control 336 also receives input from thebody temperature sensor 327.

Based on the differential between the SP1 and actual body temperature,if any, the Bulk PID control 336 raises or lowers the temperaturespecified for the heat exchange fluid that will be circulated throughthe secondary fluid circuit so as to induce a change to the patienttemperature at the specified ramp rate. That is, a value for the desiredprimary fluid temperature, or a second set point temperature (SP2), istransmitted to a primary fluid PID control unit 338 as illustrated at337. The primary fluid PID control unit 338 also receives input from thetemperature sensor 329 for the primary fluid as illustrated at 333. Theprimary fluid PID control unit 338 compares the sensed primary fluidtemperature with the desired primary fluid temperature transmitted fromthe bulk PID control to determine a differential, if any. Based on thisdifferential, the primary fluid PID control 338 transmits a digitalsignal as illustrated at 340 to an “H-Bridge” polarity switching unit342, which directs power of an appropriate magnitude and polarity to theTE cooler 348 to cause the TE heater/cooler to be heated or cooled todrive the temperature of the primary fluid to an appropriate level todrive the temperature of the secondary fluid to heat or cool thetemperature of a patient's tissue or blood toward the desiredtemperature, or maintain it at that temperature.

The polarity switching unit 342 receives power from a source 344 andtransforms that power to the appropriate magnitude and polarityrequested by the primary fluid PID control unit. Between the powersource and the polarity switching unit is a safety relay 346 actuated bythe safety system 332 that will, in the absence of a safety issue,transmit the power from the power source 344 to the polarity switchingunit 342. If the safety system 332 is aware of a safety issue, forexample if a low fluid level is sensed, it may direct the safety relay346 to open and prevent power from the power supply 344 from beingdirected to the TE cooler 348. In the absence of any safety issue,however, the polarity switching unit 342 transmits the power to theheater/cooler unit 348 in accordance to the request from the primaryfluid PID control unit. Various subsystems of the present inventionprovide input to the safety system 332, and will be described below whenintroduced.

The control circuit includes logic that permits rapid heat exchange whenthe target temperature and the sensed body temperature are relativelyfar apart, and which slows down the rate of heat exchange as the sensedbody temperature nears the target temperature. As the sensed patienttemperature and the SP1 become very close, the Bulk PID will dictateonly a very small change in the primary fluid temperature, and thus therate of change will become smaller and smaller as the SP1 becomes veryclose to the sensed patient temperature until the rate of change isessentially non-existent. In this way, the patient temperature may bevery gently is heated or cooled the last few tenths of a degree,avoiding overshoot or dramatic swings from heating to cooling when thebody temperature is at the target temperature. As the input TARGETTEMPERATURE is reached, the SP1 and the TARGET TEMPERATURE areessentially the same, and the system operates to set the power to the TEcooler at a level that maintains the necessary primary fluid circuittemperature to hold the patient temperature at the TARGET TEMPERATURE.In this way, the system will work to maintain a target temperature withthe primary fluid maintained at just the right temperature to add orremove heat at the precise rate necessary to maintain that targettemperature as essentially a steady state.

The primary fluid PID control 338 samples its respective inputs at arate of 10 times a second and updates the output to the polarityswitching unit 342 at a rate of once every second, and thus the trendsof changing patient temperature are constantly monitored and adjusted.The Bulk PID control 336 samples its inputs at the same rate, and thus anew target temperature or a new ramp rate can be specified by the userwith nearly instantaneous system response.

The controller of the present invention may also be used to controlother aspects of the cooling system. For example, in one embodiment,when the temperature of the patient approaches within 0.3 degrees of thetarget temperature, the controller may decrease the output of thesecondary fluid circuit pump, may decrease the output of the primaryfluid circuit pump, and/or reduce the speed of the fan/blower on theprimary circuit to reduce the amount of noise generated by theapparatus.

Exemplary Heat Exchange Unit

FIG. 9 is an exploded view of an exemplary embodiment of a heat exchangecassette 400 of the present invention. Heat exchange cassette 400includes a cassette section 405 containing a reservoir compartment,secondary circuit pump and a heat exchanger 410 for exchanging heatenergy between the primary and secondary fluid circuits.

Heat exchanger 410 comprises a heat exchange section 415 disposed withina cavity formed between a base plate 420 and cover 425. O-ring bushings427 are used to seal fluid passageways inside of the cavity tofacilitate fluid flow though the heat exchange section 415. The cover425 is held to the base plate 420 by connector 430, which may be athreaded screw or bolt, or other device capable of attaching the baseplate to the cover. The entire heat exchanger 410 is attached to thecassette section 405 using suitable connectors 435. FIG. 9 also showsconnectors 440 which releasably attach a mounting cover to the reservoircompartment.

The base plate 420 also includes two fluid channels (not shown), to bediscussed in more detail below. The inlet of the first fluid channelreceives secondary fluid returning from the catheter and the inlet ofthe second fluid channel receives priming fluid to fill the heatexchanger with secondary fluid before use. The outlets of both the firstand second fluid channels are fluidly connected to the inlet 429 of theheat exchanger. Heat exchanger outlet 431 is fluidly connected to thereservoir in the cassette section 405.

Also shown in FIG. 9 are a variety of fluid connectors for completingthe fluid paths of the primary and secondary fluid circuits. Forexample, connectors 445 and 450 are mounted on cover 425 and are used asinput and output ports for communicating fluid through the primarycircuit side of the heat exchanger 415. Similarly, barb 455 is disposedin the output fluid path of the secondary fluid circuit pump, andprovides for connection to the supply line that provides secondary fluidto the balloon of the catheter that is used to heat or cool a patient'sblood. Barb 460 receives the return line from the catheter and providesan input though the first fluid channel in the base plate 420 into inletof the secondary side of heat exchanger 415.

After secondary circuit fluid has flowed through heat exchanger 415, thesecondary fluid exits the heat exchanger 415 through outlet 431 andflows out barb 470 into the reservoir of cassette section 405 throughbarb 480. Barbs 465 and 469 provide access to the secondary fluidcircuit to prime the secondary fluid circuit with secondary fluid, andbarb 475 allows the reservoir in cassette section 405 to be vented.

FIGS. 10 and 10A depict an exemplary embodiment showing the secondarycircuit tubing connections to the heat exchange cassette 400. Supplytubing 505 to the balloon catheter is connected to barb 455 (FIG. 9),and return tubing 510 is connected to barb 460. As described above, barb460 is connected via the first fluid channel in base plate 420 to theinlet 429 of the secondary side of the heat exchanger. Fluid supply line515, which includes a spike 520 covered by spike cover 525, is connectedto splitter block 540. Splitter block 540 includes barb 550 which isconnected by a short length of tubing (not shown) to barb 469. A lowpressure check valve 560 is disposed between and connects barbs 545 and465. Barb 465 is fluidly connected to the second fluid channel in baseplate 420, and provides fluid access to the secondary side of the heatexchanger to allow the heat exchanger to be primed with secondarycircuit fluid when necessary. Vent line 530, which includes an active orpassive vent valve 535 is connected to barb 475.

The secondary fluid circuit may be primed with secondary fluid byinserting spike 520 into a fluid source. Fluid flows into spike 520 andthrough line 515 and into splitter 540, where the fluid stream isdivided. Fluid then flows into the heat exchanger through check valve560 and barb 465 and into the second fluid channel in base place 520 andfinally into the inlet 429 of the heat exchanger. Simultaneously, fluidflows into the reservoir of the cassette section through barb 469. Checkvalve 560 is a one way valve that allows fluid to flow during priming,but prevents flow in the opposite direction, as would occur duringoperation of the secondary fluid circuit when fluid under pressure fromthe return line would be present at the inlet of the heat exchanger.This arrangement is advantageous in that it allows the reservoir andheat exchanger to be primed simultaneously.

In another embodiment, lines 515 and 530 may include valves that may beautomatically actuated to facilitate automatic priming of the secondaryfluid circuit. In one preferred embodiment, lines 515 and 530 runthrough a electrically actuatable clamp. When the operator of the systempresses a button, for example, a PRIME button on the controller orcontroller display, the controller commands the clamp to open. At thistime, fluid flows from the fluid source into the reservoir, and air isallowed to vent from the system. Typically, the fluid from the fluidsource fills the reservoir via gravity, but a pressure cuff, or othersimilar means, may be applied to the fluid source to increase the rateof fluid flow, and thus decrease the time needed to prime the secondaryfluid circuit. When the level in the reservoir is determined to be full,utilizing the sensing system previously described, controller closes theclamp or valve controlling flow through vent line 515. The clamp orvalve on line 530 may remain open to allow the fluid source toaccommodate volume changes that occur due to temperature changes and orpressure changes in the secondary fluid circuit during operation.

FIGS. 11A and B depict additional detail of an exemplary embodiment ofthe cassette section 405. Referring to FIG. 11A, the cassette section405 is shown in the reverse orientation in which it is inserted into thecontrol unit (FIG. 2). Cassette section 405 includes a cassette block605 which, as is seen in FIG. 11B, has side walls that form a reservoir607. Also visible on the bottom surface of cassette block 605 in FIG.11A is a window 615 which provides for transmission of light beams intothe reservoir for use in determining the fluid level within thereservoir 607. Pump coupler 610 is also disposed on the bottom surfaceof the cassette block 605, and is configured to couple to pump driver 68(FIG. 2) to drive the secondary fluid circuit pump.

The top side of cassette block 605 is closed by cover 620. Cover 620 istypically opaque, and includes a mirror 625 disposed on an insidesurface of the cover 620. Mirror 625 forms part of a fluid level sensorthat is used to determine the level of secondary circuit fluid withinreservoir 607. Also shown are pump seal 630 and pump shaft bushings 635,which will be described in more detail with reference to FIG. 11B.

FIG. 11B depicts the cassette section 405 in a right side up orientationso as to facilitate discussions of additional details of the structureand components of the cassette section 405. As described above, thesides walls of cassette block 605 and the cover 620 form a secondaryfluid circuit reservoir 607 within cassette section 605. A prism 655which forms a portion of the above described level sensor is mounted onan inner surface of the cassette block, and is in light communicationwith window 615 disposed on the top surface of cassette block 605.

In an alternative embodiment, two prism may be used to provide aredundant system. In such an arrangement, the controller may also havetwo processors, one main processor and a safety processor. The mainprocessor monitors the first prism, and the safety processor monitorsthe second prism. The monitoring of the prisms may be timed by theprocessors such that the main processor should detect any abnormalitiesbefore the safety processor does. Thus, an alert may be sent to the userand the pump will stop. In this case, the pump may be restarted. If theabnormality is not corrected and is detected by the safety processor,the pump may be stopped and require intervention to determine the causeof the abnormality before treatment may proceed. Alternatively, bothsafety systems may function simultaneously and with equal priority, sothat a low level indicator by either one will trigger a signal to theuser such as an alarm, or will stop the pump.

Disposed within the reservoir 607 is secondary fluid circuit pump 660.In the depicted embodiment, pump 660 is a gear pump having a pair ofpumping gears 665 each mounted on a pump shaft 677 disposed within apump body 679. A backing plate 670 holds shafts 677 in place within thepump, and a height compensator 675, which is typically formed from acompressible material, such as a biocompatible plastic such as, forexample, silicon, is disposed on the shafts between the backing plate670 and the end of the shafts. The height compensator supplies pressureonto the pump gears to hold the gears in place while allowing somemovement of the gears so they may freely rotate. Cover 620, which isshown inverted in FIG. 11B, is held in place on cassette block 605 toform reservoir 607 using suitable connectors 680.

Also disposed in reservoir 607 is an air trap 685. Air trap 685 is madefrom a porous material that allows secondary fluid to flow through theair trap, but blocks the flow of air. Air trap 685 may be formed fromany material that preferentially allows fluid to flow but blocks theflow of air, for example, such as a semi permeable membrane or a foamblock. Although the air trap may be omitted in some embodiments of thepresent invention, use of air trap 685 is advantageous as it provides ameans for trapping air bubbles, either large of small, entrained in thesecondary circuit fluid before the fluid enters the secondary circuitpump.

In an alternative embodiment, where the cassette reservoir issufficiently isolated using luer lock connectors and check valves, thecassette reservoir may be pre-filled with secondary fluid. Providingsuch a pre-filled reservoir would eliminate the need to prime thesecondary fluid circuit with secondary fluid before operating the pump.In such an arrangement, a fluid used to fill the fluid pathways of thecatheter could be made up by attaching the priming line to a fluidsource, if necessary.

It will be understood that the pump 660 may be located on the outputside of the heat exchanger's secondary fluid circuit to push secondaryfluid through the catheter. Alternatively, the pump 660 may also belocated on the inlet side of the heat exchanger's secondary fluidcircuit.

In an alternative embodiment, a suitably flexible cooling balloon can bemounted on the catheter such that pulsations in the secondary fluidcaused by the pump result in fluctuation of the balloon. Suchfluctuation of the balloon may be advantages in promoting better heattransfer between a patient's blood and the cooling fluid in the balloonby inducing turbulence in the blood flow adjacent to the surface of theballoon.

Safety Systems

As described previously, the reservoir section can be provided with ameans to monitor the amount of heat exchange fluid that is in thesystem, more specifically an optical means for detecting the level offluid contained within the fluid reservoir. Since the secondary fluid isa biocompatible fluid and the volume of the external source is onlyabout 250 ml, it is not expected that fluid leakage into the patientwill be problematic. It would be undesirable, however, to have the fluidlevel fall so low that air is pumped into a patient. Therefore the heatexchange fluid supply system of the invention is designed to detect thelevel of the fluid in the system so that a warning or other measure canbe instituted if the system becomes unacceptably low. As shown in FIGS.11A and B, a pair of prisms 655 are mounted to the cassette block 605each having a corresponding beam source and beam, are utilized to form afluid level sensor. Each prism 655 will have a corresponding beam sourceand sensor mounted on the control unit at a location adjacent to theprism.

As seen in FIG. 11A, the transparent window 615 disposed in the bottomsurface of the cassette block 605 allows for optical monitoring of thefluid level in the reservoir 607. An adjacent beam source and sensorwould also be provided for the second prism 655, if present.

Typically, the beam source(s) and sensor(s) would be positioned on thecontrol unit at a location so as to access the interior of reservoir 607through the window 615. The prisms 655 have a diffraction surface andmay be molded or machined separately using a material such aspolycarbonate and then affixed within the reservoir section, or they maybe machined as part of the section. Again, although only one prism isneeded for the fluid level detection method to function, it may bedesirable to include a second redundant prism described below.

The second prism/source/sensor is redundant and functions to monitor thesame fluid level as the first prism but operates as a safety mechanismin the even the first prism/source/sensor fails to function properly.Alternatively, one of the prisms may also have a “high level” sensingsystem that can be used to signal the control unit when the fluid in thereservoir reaches a certain high level. This is useful, for example,when a valved-priming system is used and detection of a high or fulllevel is needed to determine when to activate the valve to stop thepriming sequence. If desired, both high level and low level sensors canbe employed on each prism. The sensors will generate a signal indicatingthat either there is or is not fluid at the level of the optical beam.If the optical beam source and sensor are positioned or the optical beamis directed near the top of the tank, the indication that the fluid hasreached that level will trigger the appropriate response from thecontrol system, for example to terminate a fill sequence. On the otherhand, if the sensor is positioned or optical beam directed to sense thefluid level on the bottom of the tank, then the fluid level detector isconfigured to detect a low fluid level and can generates a signalrepresenting such low level. The controller can then be configured torespond to this signal indicative of a low level of fluid in thereservoir. For example, the controller can be designed to be responsiveto this signal such that it controls the secondary circuit pump to stoppumping when a low fluid level is detected, so that air will not bepumped into the heat exchange catheter. In addition, an alarm may soundand an alarm display, such as the display 200 of FIG. 5C, may beactivated to alert the operator to the low fluid level condition.

In a preferred embodiment of the present invention, several levels ofsafety redundancy are provided to prevent failure of the system, andpotential injury to the patient. First, two microprocessors may beprovided and constantly monitored for agreement. If one fails, thesystem alarms and shuts. Secondly, two or more patient sensors may beprovided and monitored for agreement. They are sampled frequently by thecontroller and if the values do not agree, as with the microprocessor,the system alarms and shuts down. Likewise, two or more fluid levelsensors for the heat exchange circulation path desirably agree forredundancy. Still further, two or more temperature sensors for the heatexchange medium could be provided and monitored for agreement. In short,various redundant subsystems of the overall system ensure properoperation and the feedback therefrom is used to shut off the system ifnecessary.

In another preferred embodiment of the invention, the reservoir 607section is provided with a means to detect when the fluid reservoir istoo low. Typically, an optical beam source would begin operation afterthe reservoir fills with fluid. In operation, the optical beam sourceproduces an optical beam that is directed into the prism from the bottomand is internally reflected one or more times within the prism at itssurface interface with the fluid and back to the optical beam sensor. Aslong as fluid is in the reservoir, the sensor will observe a reflectedlight beam and the pump will continue to operate, moving fluid throughthe heat exchange cassette and catheter. However, if the fluid leveldrops below the upper reflective surfaces of the prism, thus changingthe reflective index at that internal surface, the sensor then will notobserve a reflected light beam. When no such reflected beam is received,the system sounds an alarm and ceases to pump.

Additional safety systems that are contemplated by the invention includebubble or air-in-line detectors at various locations on the conduits todetect any bubbles or entrained air that may be pumped into the fluidsystem and temperature monitors that may signal if a portion of thesystem, or the fluid, is at a temperature that is unacceptably high orlow. Moreover, the bubble or air-in-line detectors may also beconfigured to indicate whether an acceptable level of fluid is presentwithin a fluid circuit. A detector to indicate whether the fluid sensoroptical beam sources are operational may be supplied, for example byplacing a detector located to detect the optical beam initially when thesystem is turned on but there is insufficient fluid in the reservoir tocause the beam to diffract back to the detector. The control unitdepicted in FIGS. 1,2 and 5 provide for multiple patient temperaturesensors. A warning may sound, and the system may shut down, if thetemperature signal from the two different sensors are dramaticallydifferent, indicating that one of the sensors, perhaps the one drivingthe control of the system, is misplaced, is not functioning, has fallenout or the like. Other similar safety and warning systems arecontemplated within the scope of the system of the invention.

It should also be understood, in accordance with the present invention,that the controller processor may be configured to simultaneouslyrespond to multiple sensors, or to activate or de-activate variouscomponents such as several heat exchangers. In this way, for example, acontroller might heat blood that is subsequently circulated to the corebody in response to a sensed core body temperature that is below atarget temperature for the core, and simultaneously activate a secondheat exchanger to cool blood that is directed to the brain region inresponse to a sensed brain temperature that is above a targettemperature for the brain. It may be that the sensed body temperature isat the target temperature and thus the heat exchanger that is in contactwith blood circulating to the body core may be turned off by thecontroller, while at the same time the controller continues to activatethe second heat exchanger to cool blood that is directed to the brainregion. Any of the many control schemes that may be anticipated by anoperator and programmed into the control unit are contemplated by thisinvention.

One advantage of the various embodiments of the system of the presentinvention is that it provides for the exchange of a large amount of heatbetween a patient's blood and the cooling circuits. In order to ensurethat a patient's temperature may be lowered as rapidly as possible, andthen maintained, it has been found to be desirable to maintain theprimary fluid circuit at a temperature in the range of 0-5 degreescentigrade against a thermal load of greater than 400 watts. However, asthose skilled in the art will understand, maintaining the primary fluidtemperature at such a level is difficult to accomplish. FIG. 12 is agraphical representation showing how one embodiment of the presentinvention performed. This graph shows that the embodiment tested wasable to maintain a primary fluid temperature of less than 1.5 degreescentigrade under a power load of 500 watts.

FIG. 13 is a graphical representation illustrating the performance ofone embodiment of the present invention compared to the performance ofprior cooling system when used to cool patients. Line 700 was derivedusing the embodiment of the present invention, and shows how patientswere cooled to 33 degrees centigrade in an average of 19 minutes. Thiscontrasts with the prior system, depicted by line 710, which required 68minutes on average to cool a patient to 33 degrees centigrade. Thedashed lines in FIG. 13 depict the 95% confidence interval around thedata used to derive the lines 700, 710.

Another advantage of the system of the present invention is that theability to extract large amounts of heat from the primary cooling loopprovides for reduced time for the system to begin removing large amountsof thermal energy from the patient. For example, when needed, theprimary cooling loop can be cooled to its target temperature of lessthan 3 degrees centigrade in 5 minutes or less. Such rapid cooling maybe needed in an emergent situation where fast cooling of a patient isdesired but where use of such a system was not anticipated.

A further advantage of the system of the present invention is that allof the portions of the system that are in contact with the patient maybe disposable, but substantial and relatively expensive portions of thesystem are reusable. Thus, the catheter, the flow path for sterile heatexchange fluid, the sterile heat exchange fluid itself, and the pumphead are all disposable. Even if a rupture in the heat exchange balloonpermits the heat exchange fluid channels and thus the pump head to comein contact with a patient's blood, no cross-contamination will occurbetween patients because all those elements are disposable. The pumpdriver, the electronic control mechanisms, the heat exchanger, and themanual input unit, however, are all reusable for economy andconvenience. Desirably, as illustrated, all of these re-usablecomponents are housed within a single control unit that may be operatedby a single operator in the surgical or general wards of a hospital orother care giving institution. Likewise, the various sensors distributedaround body and along the catheter may be disposable, but the controllerprocessor to which they attach is re-usable without the need forsterilization.

In another embodiment of the present invention, as shown in FIG. 6,check valve 286 may be included in the primary fluid circuit to controlthe pressure within the primary fluid circuit should the outlet side ofthe primary fluid circuit be disconnected. In some embodiments, theprimary fluid circuit pump is capable of pumping the primary fluid atpressures that greatly exceed a preselected safety threshold. Forexample, the pump may be capable of reaching pressures of 50 psi ormore. To provide further safety to the patient, the check valves in theprimary fluid circuit may be chose so as to prevent the pressure withinthe primary circuit from exceeding a pressure that has been determinedto be safe, such as, for example, 35 psi. This prevents the heatexchanger from ever being exposed to a pressure that might cause afailure of the primary fluid circuit within the heat exchanger. Thisprovides for increased safety for the patient, since the pressure limitprevents the possibility of a catastrophic rupture heat exchanger fluidcircuits and thus prevents the possibility of circulation of primaryfluid, which may be a material such as alcohol or propylene glycol orthe like, into the secondary fluid circuit, through the catheter, andinto the patient.

The unique combination of fluid lines, connectors and valves providemany advantages over prior art systems. For example, where the primaryfluid connectors of the cassette include releasable couplers whichfluidly seal, the cassette may be shipped with the primary fluid circuitof the cassette full of primary cooling fluid. In another embodiment,the secondary fluid circuit of the cassette may be pre-filled withsecondary cooling fluid and sterilized, thus eliminating, or at leastsubstantially reducing, the amount of time and effort needed to primethe secondary fluid circuit.

It will also be appreciated by those of skill in the art that the systemdescribed herein may be employed using numerous substitutions,deletions, and alternatives without deviating from the spirit of theinvention as claimed below. For example, but not by way of limitation,the primary and secondary fluid pathways in the heat exchange plate maybe a bellows, tube in tube, fan folded sheet, plate, coil or othersuitable configuration, or the sensors may sense a wide variety of bodylocations and other parameters may be provided to the processor, such astemperature or pressure. Further, the in-dwelling heat exchanger at theend of the catheter may be any appropriate type, such as a non-balloonheating/cooling element. An appropriate pump might be provided that is ascrew pump, a gear pump, a diaphragm pump, a peristaltic roller pump, orany other suitable means for pumping the heat exchange fluid. All ofthese and other substitutions obvious to those of skill in the art arecontemplated by this invention.

Another embodiment of the present invention is configured to acceptsupplemental cooling devices that may be used to supplement the coolingof the primary fluid circuit, the secondary cooling circuit, or both. Inone embodiment, the supplemental cooling device comprises a vesselhaving each end sealed with an end cap. The vessel may be cylindrical,configured as a flat plate, or other suitable configuration. Theinterior of the vessel between the two end caps defines a chamber filledwith a cooling medium, which may be a liquid, such as water, a gel, or asolid such as ice or other frozen material. An inlet tube extendingthrough one of the end caps carries a first quick-disconnect fastenerfor detachably coupling the inlet tube in fluid communication with afluid source, such as the primary or secondary fluid circuit, and anoutlet tube extending through the other end cap, terminated by a secondquick-disconnect for detachably coupling the outlet tube in fluidcommunication with the primary or secondary fluid circuits. As fluidfrom the primary or secondary fluid circuits enters the inlet tube, heatenergy in the fluid is absorbed by the cooling medium, and thus thetemperature of the fluid flowing through the fluid circuit is furthercooled by the cooling device. This supplemental cooling provides for anincreased rate of temperature reduction in a patient, which may bebeneficial in certain situations. Moreover, if the amount of coolingrequired exceeds the cooling capacity of the main heater/cooler, evenwith the addition of one supplemental cooling device, additionalsupplemental cooling devices may be coupled into the primary orsecondary fluid circuits as desired. Further, the quick-disconnectcouplings allow for replacement of a supplemental cooling device thathas absorbed as much heat energy as it can with a fresh supplementalcooling device when necessary. Alternatively, other stored energysources such as compressed or liquefied gas, or endothermic reactivechemicals, may be used as supplemental cooling sources. Additionally,the system may also be configured with supplemental heating sources toaugment the heating ability of the system to address situations where apatient requires warming at a higher rate than can be provided by a TEor resistive heating element alone.

While particular embodiments of the invention have been described abovefor purposes of illustration, it will be evident to those skilled in theart that numerous variations of the above-described embodiments may bemade without departing from the invention as defined in the appendedclaims.

1-53. (canceled)
 54. A system for use for adjusting the temperature of apatient, comprising: a primary fluid circuit; a heat exchanger having aprimary fluid side and a secondary fluid side; releasable couplersconfigured to fluidly couple the primary fluid side of the heatexchanger to the primary fluid circuit; a heat exchange catheterinsertable within a patient, the heat exchange catheter having secondaryfluid circuit lines coupled to the secondary fluid side of the heatexchanger; and controller circuitry for controlling the operation of thesystem, the controller circuitry being configured to control a heaterand/or cooler to alter a value of a temperature parameter representativeof the temperature of the fluid in the primary fluid circuit.
 55. Thesystem of 54, wherein the heat exchanger is provided to an operator withthe secondary fluid side pre-filled with secondary fluid.
 56. The systemof claim 54, further comprising: releasable couplings disposed betweenthe secondary fluid circuit lines and the secondary fluid side of theheat exchanger for coupling and uncoupling the secondary fluid side ofthe heat exchanger with the heat exchange catheter.
 57. The system ofclaim 54, wherein the cooling means is a refrigerator configured to coolthe primary fluid.
 58. The system of claim 54, wherein the cooling meansand the heater means is a thermoelectric heater/cooler.
 59. The systemof claim 54, wherein the heat exchanger may be disconnected from theprimary fluid circuit and connected to a different primary circuitwithout compromising sterility or fluid isolation of the secondary fluidlines.
 60. A heat exchanger for use in a system for adjusting thetemperature of a patient, comprising: a primary fluid circuit side; asecondary fluid circuit side, the secondary fluid circuit side in fluidcommunication with a heat exchange catheter insertable within a patientand a secondary fluid circuit for flowing secondary fluid through thesecondary circuit side and the heat exchange catheter; and releasablecouplers for releasably coupling the primary fluid circuit side with aprimary fluid circuit.
 61. The heat exchanger of claim 60, wherein theprimary fluid circuit includes a primary fluid circuit pump, and whereinthe primary fluid circuit is disposed within a housing configured toreceive the primary fluid circuit side and the secondary fluid circuitside, the housing also including a microprocessor and a secondary fluidcircuit pump motor, and wherein the secondary fluid circuit sideincludes a secondary fluid circuit pump configured to releasably engagethe secondary fluid circuit pump motor when the secondary fluid circuitside is received within the housing.
 62. The heat exchanger of claim 60,wherein the secondary fluid circuit side has a secondary side inlet anda secondary side outlet, and further comprising: releasable couplingsdisposed at the secondary side inlet and outlet for coupling anduncoupling the secondary fluid circuit side with the heat exchangecatheter.
 63. The heat exchanger of claim 60, wherein the primary fluidcircuit side and secondary fluid circuit sides are disposed in acassette.
 64. The heat exchanger of claim 60, wherein the primary fluidcircuit side may be disconnected from the primary fluid circuit andconnected to a different primary circuit without compromising sterilityor fluid isolation of the secondary fluid circuit.
 65. The heatexchanger of claim 60, wherein the primary fluid side is pre-filled withprimary fluid.
 66. The heat exchanger of claim 60, wherein the secondaryfluid side is pre-filled with secondary fluid.
 67. A method foradjusting the temperature of a patient, comprising: circulating aprimary fluid in a primary fluid circuit, the primary circuit includinga primary fluid circuit pump, a primary fluid heat exchanger, andprimary fluid circuit lines connecting the primary fluid circuit pump tothe primary fluid heat exchanger such that a continuous flow path forcirculating primary fluid from the pump to the primary fluid heatexchanger and back to the pump is formed; fluidly connecting the primaryfluid circuit to a primary fluid circuit side of a second heat exchangerusing releasable couplers, the second heat exchanger also having asecondary fluid circuit side, the releasable couplers for releasablycoupling the second heat exchanger to the primary fluid circuit andwherein the releasable couplers fluidly seal when the second heatexchanger is not connected to the primary fluid circuit; providing aheat exchange catheter insertable within a patient, the catheterconfigured to increase, decrease or maintain the temperature of thepatient; circulating a secondary heat exchange fluid through thesecondary fluid circuit side of the second heat exchanger and the heatexchange catheter using a secondary fluid circuit pump for pumping thesecondary heat exchange fluid through a secondary fluid circuit formedby the secondary fluid circuit side of the second heat exchanger, theheat exchange catheter, and the secondary fluid circuit pump.
 68. Themethod of claim 67, further comprising: controlling a heater/cooler toalter a temperature of the fluid in the primary fluid circuit to obtaina predetermined temperature prior to fluidly connecting the heatexchanger to the primary fluid circuit.
 69. The method of claim 67,further comprising: controlling a heater/cooler to alter a temperatureof the fluid in the primary fluid circuit to obtain a predeterminedtemperature prior to initiation of treatment of a patient.
 70. Themethod of claim 67, wherein the primary fluid circuit includestemperature sensors disposed in the primary fluid circuit, thetemperature sensors providing signals representative of the temperatureof the primary fluid flowing into and out of the primary fluid circuitside of the heat exchanger.
 71. The method of claim 70, furthercomprising: receiving and analyzing signals from the temperaturesensors, determining a difference in the temperature of the primaryfluid flowing into and out of the cassette, and providing an alert ifthe determined difference is indicative of a problem condition.
 72. Themethod of claim 67, further comprising: filling the secondary fluidcircuit with secondary heat exchange fluid using a primary fluidcircuit.
 73. The method of claim 72, wherein the priming fluid circuitincludes a prime line and a vent line, at least of one of the prime lineand vent line having a valve, and at least one sensor for determiningwhen the secondary circuit is sufficiently filled with fluid.
 74. Themethod of claim 73, further comprising: controlling the at least one ofthe valves in the prime line and the vent line to initiate and completefilling the secondary fluid circuit with secondary fluid.